Romanian Journal of Ophthalmologyrjo.ro/wp-content/uploads/2020/04/RJO_iss1_2020.pdf · 2020. 4. 4. · the Ophthalmology field in the past few years; the possible reason being that

Romanian Journal of Ophthalmology EDITOR-IN-CHIEF Mihail Zemba, M.D., Ph.D. Bucharest, Romania

E-mail: [email protected]

ASSOCIATE EDITOR Ovidiu Musat, M.D., Ph.D. Bucharest, Romania E-mail: [email protected]

EXECUTIVE EDITOR Prof. Victor Lorin Purcarea, Ph.D. Bucharest, Romania E-mail: [email protected]

ASSISTANT EDITORS Horia Stanca, M.D., Ph.D. Bucharest, Romania E-mail: [email protected] Daniel Branisteanu, M.D., Ph.D. Iasi, Romania

E-mail: [email protected]

INTERNATIONAL EDITORIAL ADVISORY BOARD Prof. Khaled al Rakhawy, M.D., Ph.D. Cairo, Egipt Daniel Baron M.D., Ph.D. Nantes, France Prof. Zsolt Biro M.D., Ph.D. Pecs, Hungary Prof. Derald Brackmann M.D., Ph.D. Los Angeles, USA Thierry Chazalon M.D., Ph.D. Nantes, France Prof. Gabriel Coscas M.D., Ph.D. Paris, France Prof. J.J. De Laey M.D., Ph.D. Gent, Belgium Prof. Fabian Hoehn M.D., Ph.D. Pforzheim, Germany Prof. Christian Paul Jonescu-Cuypers M.D., Ph.D. Berlin, Germany

Prof. Slobodanka Latinovic M.D., Ph.D. Novi Sad, Serbia Prof. Dan Milea M.D., Ph.D. Angers, France Gabor Rado M.D., Ph.D. Budapest, Hungary Prof.Gabor Scharioth M.D., Ph.D. Recklinghausen, Germany Prof. Wolfgang Schrader M.D., Ph.D. Wuerzburg, Germany Prof. Fankhauser Franz M.D., Ph.D. Bern, Switzerland Tina Xirou, M.D., Ph.D. Athens, Greece Prof. Dr. Andreas Wedrich, M.D., Ph.D. Graz, Austria NATIONAL EDITORIAL ADVISORY BOARD Assoc.Prof. Florian Balta, M.D., Ph.D. Bucharest, Romania Prof. Dorin Chiselita M.D., Ph.D. Iasi, Romania Assoc. Prof. Mircea Filip M.D., Ph.D. Bucharest, Romania Prof. Mihnea Munteanu M.D., Ph.D. Timisoara, Romania Daniela Selaru M.D., Ph.D. Bucharest, Romania

Assoc.Prof. Cristina Stan M.D., Ph.D. Cluj Napoca, Romania Prof. Adriana Stanila M.D., Ph.D. Sibiu, Romania Cornel Stefan M.D., Ph.D. Bucharest, Romania Prof. Calin Tataru M.D.,Ph.D. Bucharest, Romania Prof. Cristina Vladutiu M.D., Ph.D. Cluj Napoca, Romania NATIONAL EDITORIAL BOARD Gheorghe Anghel M.D., Ph.D. Bucharest, Romania Eugen Bendelic M.D., Ph.D. Chisinau, Republic of Moldova Camelia Bogdanici M.D., Ph.D. Iasi, Romania Daniel Branisteanu M.D., Ph.D. Iasi, Romania Marian Burcea M.D., Ph.D. Bucharest, Romania Catalina Corbu M.D., Ph.D. Bucharest, Romania Mihaela Coroi M.D., Ph.D. Oradea, Romania Valeria Coviltir M.D., Ph.D. Bucharest, Romania Valeriu Cusnir M.D., Ph.D. Chisinau, Republic of Moldova Danut Costin M.D., Ph.D. Iasi, Romania Monica Gavris M.D., Ph.D. Cluj Napoca, Romania Karin Horvath M.D., Ph.D. Tg. Mures, Romania Sanda Jurja M.D., Ph.D. Constanta, Romania

Carmen Mocanu M.D., Ph.D. Craiova, Romania Cristina Nicula M.D., Ph.D. Cluj Napoca, Romania Monica Pop M.D., Ph.D. Bucharest, Romania Mihai Pop M.D., Ph.D. Bucharest, Romania Alina Popa-Cherecheanu M.D., Ph.D. Bucharest, Romania Vasile Potop M.D., Ph.D. Bucharest, Romania Speranta Schmitzer M.D., Ph.D. Bucharest, Romania Horia Stanca M.D., Ph.D. Bucharest, Romania Ioan Stefaniu M.D., Ph.D. Bucharest, Romania Simona Talu M.D., Ph.D. Cluj Napoca, Romania Liliana Voinea M.D., Ph.D. Bucharest, Romania Mihail Zemba, M.D., Ph.D. Bucharest, Romania PUBLISHING EDITORS Consuela Madalina Gheorghe, Bucharest, Romania Dodu Petrescu, Bucharest, Romania Petrut Radu, Bucharest, Romania

EDITORIAL OFFICE "Dr. Carol Davila"Central Military University Emergency Hospital 134 Calea Plevnei Street, District 1, Bucharest, Romania Phone number/Fax: +40.21.3137189 E-mail:[email protected], Typesetting and cover graphic: P. Radu

Volume 64, Issue 1January-March 2020

© All the rights on the journal belong to the Romanian Society of Ophthalmology. The partial reproduction of the articles or of the figures is possible only with the written consent of the Romanian Society of Ophthalmology. The responsibility of the articles’ originality belongs entirely to the authors. Print ISSN 2457 – 4325 ISSN-L 2457 - 4325

Online ISSN 2501-2533 ISSN–L 2457-4325

Printed at ''Carol Davila'' University Press, 8 Eroilor Sanitari Blvd., 050474 Bucharest, Romania

Romanian Journal of Ophthalmology Volume 64, Issue 1, January-March 2020 Contents Editorial

Sustainable practices and ophthalmological services: a caterpillar effect? Gheorghe Consuela-Mădălina

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ReviewsEye involvement in ANCA positive vasculitisMacarie Sorin Simion, Kadar Alexandra

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A meta-analysis to study the effect of pan retinal photocoagulation on retinal nerve fiber layer thickness in diabetic retinopathy patients Wadhwani Meenakshi, Bhartiya Shibal, Upadhaya Ashish, Manika Manika

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Visual evoked potential in the early diagnosis of glaucoma. Literature review Firan Anne Marie, Istrate Sînziana, Iancu Raluca, Tudosescu Ruxandra, Ciuluvică Radu, Voinea Liliana

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EMR in Eye Units Camburu Georgiana, Purcărea Victor Lorin

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Is Central Corneal Thickness a reliable independent factor in decision-making regarding the management of patients with high IOP? Camburu Georgiana, Zemba Mihail, Purcărea Victor Lorin

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General articlesClinical features, management and visual outcomes on patients with traumatic hyphema in a reference ophthalmological clinic in Colombia Galvis Virgilio, Pedraza-Concha Angelica, Tello Alejandro,Plata M. Lina , Escaf C. Luis , Berrospi D. Ruben

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Diagnosing the Dry Eye Syndrome in modern society and among patients with glaucoma: a prospective study Bulat Nina, Cuşnir Valeriu Valeriu, Procopciuc Vitalie, Cușnir Vitalie, Cuşnir Nicon Valeriu

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Evaluation of contrast sensitivity and color vision in lead and zinc mine workers Fattahi Farzaneh, Khabazkhoob Mehdi, Jafarzadehpour Ebrahim, Mirzajani Ali, Yekta AbbasAli

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Comparison of the Trend of Excimer laser refractive surgery in Provinces of Iran between 2010 and 2014 Hashemi Hassan, Saatchi Mohammad, Yekta Abbasali, Nojomi Marzieh, Asgari Soheila, Khabazkhoob Mehdi

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Case reportsComplex reconstruction of the orbitofrontal regions using three regional flaps after orbital exenteration for the treatment of basal cell carcinoma Bejinariu Cătălin Gheorghe, Dragosloveanu Christiana Diana Maria, Marinescu Silviu Adrian

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Relapsed ocular squamous surface neoplasia treated with topical interferon alfa-2b Rocha-de-Lossada Carlos, Alba-Linero Carmen, Borroni Davide, Rachwani-Anil Rahul, Zamorano-Martín Francisco, Rodríguez-Calvo-de-Mora Marina

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Suspected ocular toxocariasis and macular heterotopiaRahhal-Ortuño Miriam, Alonso-Muñoz Luis, Fonseca-Fernández Eduardo, Rahhal MS

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Retinal toxicity after facial laser epilationPlăcintă Ioan Alexandru, De Freitas-Rodríguez Angélica, Rahhal-Ortuño Miriam, Udaondo Patricia

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Orbital metastatic neuroblastoma presenting as posttraumatic exophthalmos Frunză Ana Maria, Samoilă Ovidiu

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Letter to the Editor Leber’s Hereditary Optic Neuropathy – Reply Letter to the EditorManole Cristina, Tăbăcaru Bogdana, Stanca Simona, Stanca Horia Tudor

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EDITORIAL

1 Romanian Society of Ophthalmology

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Sustainable practices and ophthalmological services: a caterpillar effect?

Nowadays, the concept “sustainability” has many meanings for different people as well as for different fields. Not until recently specialists have debated the appropriate measures to develop sustainable practices in health care services as well. Usually, in the health care services, sustainability implies a reconciliation of the environmental, social, and economic demands that determine the resource usage, so as to enable “sustainable development”— the resource model allocation that allows the delivery of actual and potential health care needs, whereas maintaining a low influence on the environment, with diminished impact on the satisfaction of the needs of future generations (United Nations, 1987). In addition, health care professionals should struggle to come up with strategies to address the changes that take place continuously at the social, environmental and economic levels, and, at the same time, try to maximize the health care consumers’ safety. In other words, according to the article “Sustainability of public health interventions: where are the gaps?” written by Walugembe DR et al., sustainability refers to “the maintenance of health benefits over time”. Moreover, the author of the book “Eye Care in Developing Nations. Fourth Edition”, Larry Schwab, affirmed that some health care specialists define sustainability as having a grant to cover the ongoing costs for the next 5 years, covering costs entirely from health care consumer revenue, or combining income sources to support medical services. However, health care services will not be sustainable if quality is not sustainable. At the same time, increasing the volume of health care consumers while maintaining quality is critical. Moreover, according to Lennox L et al., sustainable practices become efficient if their outcomes in terms of health benefits, activities or workforce capacity are maintained. The concept of sustainability as a “process” rather than an “outcome” refers to adaptation, learning and continuous development. Consequently, sustainability has gained a lot of ground and attention from the specialists in the Ophthalmology field in the past few years; the possible reason being that it represents a key strategy in creating an eye care programme, through which ophthalmological services are being delivered to health care consumers. The concept of sustainable ophthalmological services may also refer to the carbon footprint reduction strategies. The fundamental sustainable oriented directions in ophthalmological services are: leadership, core services and management, financial viability and community (http://www.v2020eresource.org/home/newsletter/news102011). Nevertheless, the process of implementing sustainable ophthalmological services starts with the needs of the health care consumers and the medical staff, but, at the same time, reducing the costs, improving health care consumer care and the health care organization credentials by elaborating and implementing social responsibility strategies. As far as reducing costs is concerned, the provision of sustainability in health care services may lead to costs recovery, Lennox L et al. state in their paper “Navigating the sustainability landscape: a systematic review of sustainability approaches in healthcare”. Recovering costs represents the ability of an organization to produce outputs of enough value so that it acquires enough inputs to continue the production and delivery at a steady or growing rate. Further, improving health care consumer care should be the main priority of the health care organizations and prevention is the best sustainable key action.

DOI:10.22336/rjo.2020.1

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Last but not least, Walugembe DR et al. concluded that the main reasons for adopting sustainable strategies should become a priority for specialists in ophthalmological services because the sustained programmes’ long-term effects are easier to investigate since they are often maintained over a longer period of time; health care changes in a community become visible after 3-10 years after the beginning of the sustainable programmes; a focus on sustainability needs the consideration of the potential loss of investments for organizations and people, and the discontinuation of interventions without sustained benefits of any kind; discontinuation of interventions without planning or intention triggers a disillusionment effect for the participants and raises obstacles for future community mobilization efforts. Assist. Prof. Gheorghe Consuela-Mădălina, PhD,

Philologist, Authorized translator

Romanian Journal of Ophthalmology, Volume 64, Issue 1, January-March 2020. pp: 3-7

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Eye involvement in ANCA positive vasculitis Macarie Sorin Simion*, Kadar Alexandra** *Department of Ophthalmology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania **Department of Ophthalmology, County Clinical Hospital Cluj-Napoca, Romania Correspondence to: Sorin Macarie, MD, PhD, Department of Ophthalmology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, 8 Victor Babeș Street, Code: 400012, Cluj-Napoca, Romania, Mobile phone: +40722 499 041, E-mail: [email protected] Accepted: January 12th, 2020

Abstract Vasculitis is a heterogeneous group of diseases that implies the presence of necrosis and inflammation in the walls of blood vessels. The mechanisms involved are the following: immune complexes, endothelial cell antibodies, and anti-lysosomal antibodies. The immune reactions can be triggered by these mechanisms: immune complexes, endothelial cell antibodies, and anti-lysosomal antibodies. Antineutrophil cytoplasmic antibodies (ANCA) have an essential role in the following so-called ANCA+ vasculitis. Regarding this issue, we proposed to present the various aspects of ocular involvement in the ANCA+ vasculitis. Keywords: ANCA positive vasculitis, granulomatosis, polyangiitis, necrosis, inflammation, blood vessels

Introduction Vasculitis is a heterogeneous group of diseases that implies the presence of necrosis and inflammation in the walls of blood vessels. The immune reactions can be triggered by these mechanisms: immune complexes, endothelial cell antibodies, and anti-lysosomal antibodies. Antineutrophil cytoplasmic antibodies (ANCA) have an essential role in the following so called ANCA+ vasculitis: Wegener’s granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome [1-3]. The c-ANCA antibodies have a high specificity for proteinase 3 antigen (PR3). Factors such as infections, allergens exposure, irritants and emissions cause the production of proinflammatory cytokines by neutrophils and the cytokines induce the extravasation of

granules from intracytoplasmic proteins, which serve as antigens for c-ANCA antibodies: PR3- from Wegener granulomatosis (85-90%), microscopic polyangiitis (45%), Churg-Strauss syndrome (10%) and MPO from Churg-Strauss syndrome, Microscopic polyangiitis. The morphology of adhesion molecules of neutrophils will change due to antigen-antibody interaction, causing neutrophils to adhere to the endothelial cells. This will determine the release of reactive species of oxygen, proteolytic enzymes and complement activation proteins, which will injure the endothelium and will stimulate the neutrophils to secrete supplementary proinflammatory cytokines. The injury of vascular wall is followed by fibrin deposition caused by plasmatic coagulation factors, resulting in fibrinoid necrosis.

DOI:10.22336/rjo.2020.2

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Classification of Vasculitis [4]: • Immune complex mediated small vessel vasculitis: cryoglobulinemia, Henoch-Schonlein purpura (Ig A vasculitis), cutaneous leukocytoclastic vasculitis; • ANCA+ small vessel vasculitis: Wegener granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis;

• Medium vessels vasculitis: nodosa polyarteritis, Kawasaki disease; • Large vessels vasculitis: Takayasu arteritis, big cell arteritis.

ANCA+ vasculitis is characterized by necrotizing vasculitis with or without minimum immune deposits. ANCA+ vasculitis predominantly affects small vessels such as capillaries, venules, arterioles, or small arteries and it is associated with pANCA/ antiMPO or cANCA/ antiPR3 antibodies, not all patients are ANCA+. Granulomatosis with polyangiitis is a multisystemic autoimmune disease characterized by the triad: necrotizing granulomatous vasculitis, which affects superior and inferior respiratory tract, segmental and focal glomerulonephritis, and necrotizing small vessels vasculitis. Antiproteinase 3

antineutrophil cytoplasmic antibodies are present [5]. Peripheral nervous system and joints can also be affected. There are ocular and orbital symptoms in 15% of the cases at the first assessment and in 50% of the cases during the illness. The symptomatology includes orbital cellulitis, dacryocystitis, dacryoadenitis, and peripheral ulcerative keratitis. Scleritis of any type is frequent - particularly diffuse anterior or necrotizing disease, with or without peripheral ulcerative keratitis, affecting up to 40% of the patients with Wegener granulomatosis; posterior scleritis has also been reported. 10% of the patients with Wegener granulomatosis and ocular involvement have been reported to have

Fig. 1 Definitions of vasculitis adopted by the 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitis for ANCA+. Source: J.C. Jennette, R.J. Falk, P.A. Bacon, N. Basu, M.C. Cid, F. Ferrario, L.F. Flores-Suarez et al. Arthritis & Rheumatism. An Official Journal of the American College of Rheumatology. Vol. 65, No. 1, January 2013, pp 1-11. DOI 10.1002/art 37715. 2013, American College of Rheumatology

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an associated nonspecific unilateral or bilateral anterior, intermediate, or posterior uveitis, with varying degrees of vitritis. The retinal vascular manifestations range from relatively benign cotton-wool spots, with or without associated intraretinal hemorrhages, to more severe vaso-occlusive disease, including branch or central retinal artery or vein occlusion.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) - GEPA is a rare systemic necrotizing and granulomatous vasculitis (2,5 cases: 100 000 adults) that affects small-to-medium-sized vessels and is associated with severe asthma, blood and tissue eosinophilia, paranasal sinusitis, mononeuritis multiplex or polyneuropathy, histological proof of vasculitis with extravascular eosinophils.

HLA-DRB4 positivity may be a genetic risk factor for the development of Churg-Strauss syndrome and may increase the likelihood of vasculitic manifestations of the disease. The cause of this allergic angiitis and granulomatosis is unknown. No data have been reported regarding the role of immune complexes or cell-mediated mechanisms in this disease, although autoimmunity is evident with the presence of hypergammaglobulinemia, increased levels of immunoglobulin E, rheumatoid factor, and ANCA [6]. Oculoorbital involvement is characterized by pseudotumoral inflammation of the orbit. Takanashi et al. [6] distributed the ocular manifestations of Churg-Strauss in 2 groups: - Inflammatory pseudotumor type with chronic onset, positive conjunctival

Fig. 2 Ocular involvement in granulomatosis with poliangiitis

Scleritis

Peripheral ulcerative keratitis

Retinitis

Occlusion of retinal vessels

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involvement, abnormalities in orbital imaging studies, and good visual prognosis. - Ischemic type is characterized by sudden onset, no conjunctival involvement, or abnormalities in imaging studies, positive ANCA, and occasional poor visual prognosis.

Microscopic polyangiitis - PAN consists of necrotizing vasculitis with or without immune deposits (in the presence of immune deposits, mainly small vessels will be affected) necrotizing arteritis affecting small or medium vessels. Granulomatous inflammation is absent. PAN is a systemic vasculitis characterized by episodic subacute or chronic inflammation of necrotic muscular tissue and media of small arteries. It does not affect arterioles, capillaries, venules. ANCA+ suggests the diagnosis [7]. For the diagnosis of PAN, 3 out of the 10 criteria must be met/ fulfilled: weight loss of more than 4 kg, livedo reticularis, testicular pain or tenderness, myalgia, weakness, or leg tenderness, mononeuropathy or polyneuropathy, elevated diastolic blood pressure, elevated blood urea, positive hepatitis B serology, abnormal arteriographic findings, demonstration of neutrophils on biopsy specimens of small or medium-sized arteries.

A

B

C

D

Fig. 3 Retinal involvement in granulomatosis with poliangiitis

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Ocular involvement is characterized by peripheral ulcerative keratitis: peripheral corneal infiltration, corneal ulcer, and focal corneal thinning. It is considered an autoimmune disease if there is no other evident pathology. In patients with an underlying autoimmune disease, there is immune complex deposition in peripheral cornea. Diseased epithelium, keratocytes, and recruited inflammatory cells may result in the release of matrix metalloproteinases that degrade collagen and the extracellular matrix. Autoantibodies may target sites in the corneal epithelium. Retinal involvement is characterized by: intraretinal hemorrhage (Fig. 2D), cotton-wool spots, macular star and papillary edema Fig. 2A,B). Choroidal infarcts with exudative retinal detachment secondary to vasculitis involve the posterior ciliary arteries and choroidal vessels. Elschnig spots (Fig. 2C) can be observed in the posterior pole as a result of choroidal ischemia. Conclusions Ocular surface manifestations and posterior segment manifestations were major eye presentations in patients with pANCA-associated vasculitis. ANCA testing including both pANCA and cytoplasmic pattern antineutrophil cytoplasmic antibody would help establish a systemic diagnosis in patients with eye manifestations such as scleritis, retinal vein occlusion, optic neuropathy, or APMPPE. Eye involvement represents a common finding in patients with systemic autoimmune diseases, particularly rheumatoid arthritis, Sjogren syndrome, seronegative spondyloarthropathy, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The eye is a privileged immune site, but commensal bacteria are found on the ocular surface. The International Consensus Statement recommends testing and reporting ANCA using indirect immunofluorescence with immunoassay method that detects ANCA specificities for MPO and PR3. References 1. Sablé-Fourtassou R, Cohen P, Mahr A, Pagnoux C. Antineutrophil Cytoplasmic Antibodies and the Churg-Strauss Syndrome. Ann Intern Med. 2005; 143(9).

2. Boomsma MM, Stegeman CA, van der Leij MJ, Oost W, Hermans J, Kallenberg CG, et al. Prediction of relapses in Wegener’s granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study. Arthritis Rheum. 2000; 43(9):2025–33. 3. Kemna MJ, Damoiseaux J, Austen J, Winkens B, Peters J, van Paassen P et al. ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol. 2015 Mar; 26(3):537–42. 4. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan; 65(1):1–11. 5. Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, St Clair EW et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med. 2007 Nov 6. 6. Takanashi T, Uchida S, Arita M, Okada M, Kashii S. Orbital inflammatory pseudotumor and ischemic vasculitis in Churg-Strauss syndrome: report of two cases and review of the literature. Ophthalmology. 2001 Jun; 108(6):1129-33. 7. Jennette JC, Falk RJ. ANCA Vasculitis: Microscopic Polyangiitis. Wegener's Granulomatosis, and Churg-Strauss Syndrome Pathology Case Reviews. September-October 2007; 12(5):200-204.


REVIEW


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A meta-analysis to study the effect of pan retinal photocoagulation on retinal nerve fiber layer thickness in

diabetic retinopathy patients Wadhwani Meenakshi*, Bhartiya Shibal**, Upadhaya Ashish***, Manika Manika* *Chacha Nehru Bal Chikitsalya, Geeta Colony, New Delhi, India **Glaucoma Unit, Fortis Hospital, Gurugram, India ***All India Institute of Medical Sciences, India Correspondence to: Meenakshi Wadhwani, MS ophthalmology, Assistant professor Ophthalmology Chacha Nehru Bal Chikitsalya, Geeta Colony, New Delhi, Room No. 228, Chacha Nehru Bal Chikitsalya, Geeta Colony, New Delhi, India, E-mail: [email protected] Accepted: July 1st, 2019

Abstract Background. Diabetic retinopathy is a microvascular disease, it is associated with changes in peripapillary retinal nerve fiber layer thickness, these changes being more pronounced in PDR (Proliferative diabetic retinopathy) patients undergoing laser photocoagulation. Objective. To assess changes in peripapillary retinal nerve fiber layer thickness in proliferative diabetic retinopathy patients using optical coherence tomogram (OCT). Methods. The database search was conducted in June 2018 and continued until October 2018. The search engines used included Pubmed, Medline, OVID and Google Scholar. A meta-analysis of weighted mean difference and standard deviation was conducted. Results. A total of 10 studies containing 377 eyes of PDR patients were selected. The analysis of the included studies revealed no significant effect of PRP on average retinal nerve fiber layer thickness (0.249, 95% CI: -0.985 to 1.483) using OCT. Conclusion. Hence, to conclude, our meta-analysis revealed that there was no significant effect of PRP on RNFL thickness and the impact of PRP could vary. Measurement of peripapillary RNFL thickness may yield erroneous and unpredictable results in this subgroup of patients, further confounding the evaluation of nerve fiber layer damage and its progression. Keywords: diabetic retinopathy, panretinal photocoagulation, retinal nerve fiber layer thickness

Introduction Diabetic retinopathy (DR) is the leading cause of blindness worldwide, especially in individuals between 20 and 65 years old. The backbone of treatment of diabetics is disability limitation, and, to an ophthalmologist, this implies prevention of the visual complications due to DR and once developed, prevention of

their progression. According to the early treatment of diabetic retinopathy study (ETDRS), pan-retinal photocoagulation (PRP) is the treatment of choice for proliferative diabetic retinopathy (PDR) and severe non-proliferative diabetic retinopathy (severe NPDR). PRP reduces chances of profound vision loss by half in these types of patients [1-4].

DOI:10.22336/rjo.2020.3

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There are several studies that confirmed the reduction of visual acuity even after PRP and this may be attributed to macular edema. In addition, it must be kept in mind that even though PRP mainly impacts the retinal photoreceptors and RPE, its effect may cause irreversible changes in the other inner retinal layers, as well as the RNFL. Mechanism of action and rationale for

review Laser light used in PRP is primarily absorbed by melanosomes in retinal pigment epithelium (RPE), leading to photocoagulation of RPE cells and adjacent photoreceptors. As the photoreceptors are highly active metabolically, the immediate effect of this is that reduction in oxygen (O2) consumption of outer retina and diffusion of O2 from choroid to inner layers of retina occurs by creating photoreceptor free window defects and also reduction occurs in ischaemia and ischaemia induced angiogenic factors. Although diabetic PRP helps salvage the vision, it is also associated with some grave complications in the form of higher intensity lasers leading to destruction of the entire retinal layer including ganglion cells leading to decrease in RNFL thickness. If laser intensity is too high, it can destroy the entire retinal layer including ganglion cells, leading to a decrease in RNFL thickness. Mild retinal edema can result immediately after PRP, due to increased retinal inflammation caused by increasing vascular permeability [5-10]. DM itself can cause reduction in RNFL thickness by apoptosis of neuronal cells. In addition, decrease in retinal nerve fiber layer thickness after PRP in diabetic patients can occur due to glycosylation end products of diabetes and thermal damage from photocoagulation of retina. The prolonged assault on the retinal nerve fiber layer thickness in patients undergoing PRP for DR means that the serial monitoring of these patients requires a careful interpretation. Any decrease in RNFL thickness in patients post PRP may be therefore due to one of four reasons: 1. Damage to retinal layer including ganglion cells due to dissipation of laser energy and consequent thermal damage;

2. Reduction in RNFL thickness by apoptosis of neuronal cells in time; 3. Reduction in RNFL thickness by apoptosis of neuronal cells as a result of continuous low-grade inflammation due to glycosylation end products of diabetes; 4. Due to comorbidity like glaucoma. It is imperative to critically evaluate the impact of PRP on the RNFL layer in patients with diabetic retinopathy [11-14]. RNFL imaging can be performed using optic disc cube protocol that images an area of 6 mm x 6 mm with 200 x 200 scans. The inbuilt software recognizes the center of the optic nerve by utilizing a graph-based method and a circle of 3.46 mm is positioned automatically around the optic disc center to generate average and clock hour parapapillary RNFL measurements. In this meta-analysis, only the average RNFL thickness was evaluated, and only the studies with signal strength of seven or more were included for analysis [14-20]. Materials and Methods

Search Strategy The database search was conducted in June 2018 and continued until October 2018. The search engines used included Pubmed, Medline, OVID, and Google Scholar. The following medical subject heading (MeSH) was searched separately and then cross matched: Diabetes, Proliferative diabetic retinopathy (PDR), Pan retinal photocoagulation (PRP), average retinal nerve fiber layer thickness, Optical coherence tomogram (OCT), while limiting the search to English and human studies. From the initial MeSH searches, original articles that were published after January 2000 were analyzed. Study selection The inclusion criteria for various articles was proliferative diabetic retinopathy patients treated with pan retinal photocoagulation undergoing average retinal nerve fiber layer thickness measurement pre PRP using optical coherence tomogram and followed up at 6 months for measurement of post PRP RNFL thickness using OCT.

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The exclusion criteria were: 1. Studies having no proper quantitative RNFL thickness measurement in the form of mean and standard deviation, 2. Studies without proper follow up at 6 months, 3. Studies without preoperative RNFL thickness and only postoperative RNFL thickness. 4. If the measuring tool was different from OCT. Two reviewers (M.W; M) discussed and evaluated each of the studies based on the aforementioned criteria, and any disagreement was resolved by further discussion. Data Extraction Finally, the studies retrieved were analyzed by two reviewers (MW, M) independently including first author for year of publication, location, number of subjects, type and duration of diabetes, mean age, gender, type of measuring tool, average RNFL thickness, duration of follow up. Quality Assessment The New Castle Ottawa scale (NOS) considerations were applied to each of the included studies for judging their quality. This included the criteria for subject selection, and the comparability of outcomes, as well as the case and control groups. A score of six or more indicated a study of acceptable high quality. MW and SB carried out the assessment and to arrive at an agreement.

Statistical Analysis All the studies were arranged according to the year of publication in ascending order [21-30], the mean and was recorded in the form of continuous variables, and the difference in the weighted mean and standard deviation was then calculated. The average RNFL thickness pre and post PRP was obtained as continuous variables to calculate WMD and standard deviation. Heterogeneity of the studies was calculated by Chi square test and Higgins I2 test. The fixed effect analysis was implied if the heterogeneity was not significant (p > 0.10, I2 < 50%) otherwise random effect analysis was used. Funnel plot was also designed with the help of above data. Sensitivity analysis was performed subsequentially and one study was excluded. Then the WMD in RNFL of the remaining studies was calculated again. A p value of < 0.05 was considered significant. Results

Characteristics of included studies The average RNFL thickness difference in diabetic patients with PDR undergoing PRP either by conventional or PASCAL PRP, before and after PRP, was analyzed using OCT. Finally, ten studies fitted the inclusion criteria. The included studies were from 2010 to 2017 (Table 1).

Table 1. Mean and standard deviation of RNFL thickness of diabetic patients undergoing conventional PRP (pre-PRP and post-PRP) in studies using OCT

Meta-analysis The difference in the RNFL thickness at baseline and after six months following the PRP was calculated using OCT. In the ten studies included, the heterogeneity of studies used in this meta-analysis was not found to be


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statistically significant (p=0.692, I2 = 30.3%). The studies revealed no significant effect of PRP on retinal nerve fibre layer thickness (0.249, 95% CI: -0.985 to 1.483) using OCT. The funnel plot suggested the absence of any obvious publication bias (Table 2, Fig. 1,2). Table 2. Meta-analysis of average retinal nerve fiber layer thickness in different studies in diabetic retinopathy patients using OCT

Author Effect size 95% CI 100% weight Muqit et al. [21] -4.00 -21.12 13.12 0.52 Kim et al. [22] 2.60 -3.37 8.57 4.30 Lee et al. [23] 7.50 0.82 14.17 3.44 Eren et al. [24] -5.50 -13.07 2.07 2.65 Kim et al. [25] 5.10 0.34 9.86 6.75 Park et al. [26] -0.500 -1.89 0.89 78.45 Aditi et al. [27] 5.60 -8.211 19.41 0.80 Goh et al. [28] 2.20 -15.78 20.18 0.47 Yazdani et al. [29] -2.00 -14.31 10.31 1.00 Shin et al. [30] 4.80 -4.99 14.59 1.60

Overall (I-squared = 36.8%, p = 0.114)

Lee et al,2013

Park et al,2014

ID

Yazdani et al,2016

Muqit et al,2010

Eren et al,2014

Kim et al,2014

Aditi et al,2016

Shin et al,2017

Kim et al,2013

Goh et al,2016

Study

0.27 (-0.97, 1.50)

7.50 (0.82, 14.18)

-0.50 (-1.90, 0.90)

ES (95% CI)

-2.00 (-14.32, 10.32)

-4.00 (-21.13, 13.13)

-5.50 (-13.08, 2.08)

5.10 (0.34, 9.86)

5.60 (-8.21, 19.41)

4.80 (-5.00, 14.60)

2.60 (-3.37, 8.57)

2.20 (-15.78, 20.18)

100.00

3.44

78.45

Weight

1.01

0.52

2.67

6.75

0.80

1.60

4.30

0.47

%

0.27 (-0.97, 1.50)

7.50 (0.82, 14.18)

-0.50 (-1.90, 0.90)

ES (95% CI)

-2.00 (-14.32, 10.32)

-4.00 (-21.13, 13.13)

-5.50 (-13.08, 2.08)

5.10 (0.34, 9.86)

5.60 (-8.21, 19.41)

4.80 (-5.00, 14.60)

2.60 (-3.37, 8.57)

2.20 (-15.78, 20.18)

100.00

3.44

78.45

Weight

1.01

0.52

2.67

6.75

0.80

1.60

4.30

0.47

%

0-25 -20 -15 -10 -5 0 5 10 15 20 25

Fig. 1 Meta-analysis of selected studies using OCT



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02

46

810

s.e.

of d

if

-20 -10 0 10 20dif

Funnel plot with pseudo 95% confidence limits

Discussion The purpose of the meta-analysis was to ascertain the impact of PRP on average RNFL thickness using optical coherence tomography on average retinal nerve fiber layer thickness using OCT. The OCT technology evolved from the earlier time domain system to spectral domain system. The SD OCT has been shown to produce a better scan quality, pre-perimetric RNFL defects, with better test retest reproducibility. Various authors have used the TD-OCT to report a significant decrease in average RNFL two years after the photocoagulation [19,20]. These studies reported an initial increase in RNFL until six months after photocoagulation, with RNFL thickness measurements becoming the same as at baseline at one year. They have then reported a significant drop at two years follow-up [16,17]. Some of the newer studies

have used SD-OCT for the evaluation of RNFL thickness. Although the effect of diabetes on retinal nerve fiber layer thickness has been studied in literature in past and few studies have reported decrease in thickness of RNFL even in the absence of a history of PRP [16,17]. It is noteworthy that this observation has not been consistently reported by authors who have used the OCT to measure RNFL [8,9]. Therefore, due to such inconsistent and variable results using the same tool of OCT, we planned to perform a meta-analysis. Authors have variably postulated that this fluctuation in RNFL thickness can be attributed to the PRP induced retinal inflammation and edema in the early post-PRP phase and subsequent degeneration of RNFL by retinal cell loss in the late–post-PRP phase. An increase in leukocyte rolling and subsequent augmentation of vascular permeability, resulting in retinal

Fig. 2 Funnel plot of selected studies using OCT


13


edema after PRP. On the other hand, Tso et al. have demonstrated that the high-intensity laser beam results in the damage of the entire retinal layer, including the retinal ganglion cells [31]. In addition, the reduction in the RNFL thickness by apoptosis of neuronal cells, and the damage due to glycosylation end products of diabetes also play a role [32-35]. The interplay of these heterogeneous factors which results in the final impact of PRP on the RNFL, in any individual patient, was possible. Hence, to conclude, our meta-analysis revealed that there was no significant effect of PRP on RNFL thickness and the impact of PRP could be variable. The RNFL thickness, often tends to yield erroneous and unpredictable results in this subgroup of patients, further confounding the evaluation of nerve fiber layer damage and its progression. Therefore, clinicians should keep in mind these points when interpreting the thickness in diabetics who have received PRP. It makes sense that diabetics undergoing PRP require more attention regarding neurodegenerative changes of the retinal nerve fiber layer and the resultant damage to vision. Multicenter studies, with a larger sample size may help understand the complexity of RNFL changes following PRP. Limitation of the study There are certain limitations in this meta-analysis. Even though we did not limit our analysis to location or evaluation methods during our database search, we included only those studies that were in English. We did not limit our analysis to the type of OCT used, and studies using both TD- and SD-OCT have been included in the analysis. Also, we did not restrict ourselves to scanning circle of 3.4 to 3.6 mm as done in other studies, because this was not defined in the two studies. Additionally, the type of diabetes mellitus, duration of disease and glycemic control could be possible confounding factors, none of which has been considered in this analysis.

Conflict of Interest The authors declare no conflict of interest. The study was conducted according to the Declaration of Helsinki. No funds were used to perform the study.

References 1. Ghassemi F, Ebrahimiadib N, Roohipoor R, Moghimi S, Alipour F. Nerve fiber layer thickness in eyes treated with red versus green laser in proliferative diabetic retinopathy: short term results. Ophthalmologica. 2013; 230:195-200. 2. The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. Ophthalmol. 1981; 88:583-600. 3. Cankaya AB, Ozdamar Y, Ozalp S, Ozkan SS. Impact of panretinal photocoagulation on optic nerve head parameters. Ophthalmologica. 2011; 225:193-199. 4. Singh H, Garg S, Sharma R, Vankatesh P, Saxena R, Dada T. Evaluation of the effect of panretinal photocoagulation on optic nerve head parameters using HRT3. Glaucoma. 2014; 23:7. 5. Ritenour RJ, Kozousek V, Chauhan BC. The effect of panretinal photocoagulation for diabetic retinopathy on retinal nerve fibre layer thickness and optic disc topography. Br J Ophthalmol. 2009; 93:838-839. 6. Kim HY, Cho HK. Peripapillary retinal nerve fiber layer thickness change after panretinal photocoagulation in patients with diabetic retinopathy. Korean J Ophthalmol. 2009; 23:23-6. 7. Kanamori A, Nagai-Kusuhara A, Escaño MF, Maeda H, Nakamura M, Negi A. Comparison of confocal scanning laser ophthalmoscopy, scanning laser polarimetry and optical coherence tomography to discriminate ocular hypertension and glaucoma at an early stage. Graefes Arch Clin Exp Ophthalmol. 2006; 244(1):58-68. 8. Schulze A, Lamparter J, Pfeiffer N, Berisha F, Schmidtmann I, Hoffmann EM. Comparison of Laser Scanning Diagnostic Devices for Early Glaucoma Detection. J Glaucoma. 2015; 24(6):442-447. 9. Ozdek S, Lonneville YH, Onol M, Yetkin I, Hasanreisog lu BB. Assessment of nerve fiber layer in diabetic patients with scanning laser polarimetry. Eye. 2002; 16(6):761-765. 10. Petrovic V, Bhisitkul RB. Lasers and diabetic retinopathy: the art of gentle destruction. Diabetes Technol Ther. 1999; 1(2):177-187. 11. Levin LA. Retinal ganglion cells and neuroprotection for glaucoma. Surv Ophthalmol. 2003; 48:S21–S24. 12. Grewal DS, Sehi M, Paauw JD, Greenfield DS. Advanced Imaging in Glaucoma Study Group. Detection of progressive retinal nerve fiber layer thickness loss with optical coherence tomography using 4 criteria for functional progression. J Glaucoma. 2012; 21(4):214-220. 13. Medeiros FA, Zangwill LM, Alencar LM, Bowd C, Sample PA, Susanna R Jr., Weinreb RN. Detection of glaucoma progression with stratus OCT retinal nerve fiber layer, optic nerve head, and macular thickness measurements. Invest Ophthalmol Vis Sci. 2009; 50:5741-5748. 14. Ahmed S, Khan Z, Si F, Mao A, Pan I, Yazdi F, Tsertsvadze A, Hutnik C, Moher D, Tingey D, Trope GE, Damji KF, Tarride JE, Goeree R, Hodge W. Summary of Glaucoma Diagnostic Testing Accuracy: An Evidence-



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Based Meta-Analysis. J Clin Med Res. 2016; 8(9):641-649. 15. Moreno-Montañés J, Olmo N, Alvarez A, García N, Zarranz-Ventura J. Cirrus high-definition optical coherence tomography compared with Stratus optical coherence tomography in glaucoma diagnosis. Invest Ophthalmol Vis Sci. 2010; 51(1):335-343. 16. Sugimoto M, Sasoh M, Ido M, Wakitani Y, Takahashi C, Uji Y. Detection of early diabetic change with optical coherence tomography in type 2 diabetes mellitus patients without retinopathy. Ophthalmologica. 2005; 219:379–385. 17. Mwanza JC, Chang RT, Budenz DL, Durbin MK, Gendy MG, Shi W, Feuer WJ. Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes. Invest Ophthalmol Vis Sci. 2010; 51:5724–5730. 18. Fu R, Vandermeer BW, Shamliyan TA, O’Neil ME, Yazdi F, Fox SH, Morton SC. Handling Continuous Outcomes in Quantitative Synthesis. Methods Guide for Comparative Effectiveness Reviews. (Prepared by the Oregon Evidence-based Practice Center under Contract No. 290-2007-10057-I.) AHRQ Publication No. 13-EHC103-EF. Rockville, MD: Agency for Healthcare Research and Quality. July 2013. 19. Lee DE, Lee JH, Lim HW, Kang MH, Cho HY, Seong M. The effect of pattern scan laser photocoagulation on peripapillary retinal nerve fibre layer thickness and optic nerve morphology in diabetic retinopathy. Korean J Ophthalmol. 2014; 28:408-416. 20. Nonaka A, Kiryu J, Tsujikawa A et al. Inflammatory response after scatter laser photocoagulation in nonphotocoagulated retina. Invest Ophthalmol Vis Sci. 2002; 43:1204-1209. 21. Muqit MM, Wakely L, Stanga PE, Henson DB, Ghanchi FD. Effects of conventional Argon panretinal laser photocoagulation on retinal nerve fibre layer and driving visual fields in diabetic retinopathy. Eye. 2010; 24:1136-42. 22. Kim J, Woo SJ, Ahn J, Park KH, Chung H, Park KH. Long-term temporal changes of peripapillary retinal nerve fiber layer thickness before and after panretinal photocoagulation in severe diabetic retinopathy. Retina. 2012; 32:2052-2060. 23. Lee SB, Kwag JY, Lee HJ, Jo YJ, Kim JY. The longitudinal changes of retinal nerve fiber layer thickness after panretinal photocoagulation in diabetic retinopathy patients. Retina. 2013; 33(1):188-193. 24. Eren S, Ozturk T, Yaman A, Oner H, Saatci AO. Retinal nerve fiber layer alterations after photocoagulation: A prospective spectral-domain OCT study. The Open Ophthalmol J. 2014; 8:82-86. 25. Kim JJ, Im JC, Shin JP, Kim IT, Park DH. One-year follow-up of macular ganglion cell layer and peripapillary retinal nerve fibre layer thickness changes after panretinal photocoagulation. Br J Ophthalmol. 2014; 98(2):213-217. 26. Park YR, Jee D. Changes in peripapillary retinal nerve fiber layer thickness after pattern scanning laser photocoagulation in patients with diabetic retinopathy. Korean J Ophthalmol. 2014; 28(3):220-225.

27. Aditi M, Ranjana M, Monisha NE, Carol CY, Nia M, Valencia F, Shamira P. The effect of PASCAL panretinal photocoagulation on the peripapillary retinal nerve fibre layer. J Clin Exp Ophthalmol. 2016; 7:4. 28. Goh SY, Ropilah AR, Othmaliza O, Mushawiahti M. Retinal nerve fiber layer thickness changes after pan-retinal photocoagulation in diabetic retinopathy. Journal of Surgical Academia. 2016; 6(1):4-9. 29. Yazdani S, Samadi P, Pakravan M, Esfandiari H, Ghahari E, Nourinia R. Peripapillary RNFL Thickness Changes after Panretinal Photocoagulation. Optom Vis Sci. 2016; 93(9):1158-1162. 30. Shin JS, Lee YH. Changes in Macular Retinal Layers and Peripapillary Nerve Fiber Layer Thickness after 577-nm Pattern Scanning Laser in Patients with Diabetic Retinopathy. Korean J Ophthalmol. 2017; 31(6):497–507. 31. Tso MO, Wallow IH, Elgin S. Experimental photocoagulation of the human retina: I. Correlation of physical, clinical, and pathologic data. Arch Ophthalmol. 1977; 95:1035-1040. 32. Wagdy FM, Sobky HME, Sarhan AERE, Hafez MA. Evaluation of retinal nerve fibre layer thickness in diabetic retinopathy by optical coherence tomography after full scatter panretinal argon laser photocoagulation. J. Of Egyptian Ophthalmological Society. 2013; 106:153-158. 33. Lim MC, Tanimoto SA, Furlani BA, Lum B, Pinto LM, Eliason D, Prata TS, Brandt JD, Morse LS, Park SS, Melo LA Jr. Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance. Arch Ophthalmol. Jul. 2009; 127(7):857-862. 34. Parikh RS, Parikh SR, Sekhar GC, Prabakaran S, Babu JG, Thomas R. Normal age related decay of retinal nerve fiber layer thickness. Ophthalmology. 2007; 114:921–926. 35. Maeshima K, Utsugi Sutoh N, Otani T et al. Progressive enlargement of scattered photocoagulation scars in diabetic retinopathy. Retina. 2004; 24(4):507-11.24.


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Visual evoked potential in the early diagnosis of glaucoma. Literature review

Firan Anne Marie*, Istrate Sînziana** ***, Iancu Raluca**, Tudosescu Ruxandra***, Ciuluvică Radu****, Voinea Liliana** *Barnsley District Hospital, NHS Trust, Barnsley, South Yorkshire, Great Britain **Ophthalmology Department, University Emergency Hospital Bucharest, Bucharest, Romania ***Ophthalmology Department, Regina Maria - Health Private Care, Bucharest, Romania ****Anatomy Department, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Correspondence to: Istrate Sînziana, MD, PhD, University Emergency Hospital Bucharest, Bucharest 169 Splaiul Independenței Street, District 1, Bucharest, Romania, Mobile phone: +40726 535 515, E-mail: [email protected] Accepted: January 14th, 2020

Abstract Visual evoked potentials (VEP) are a significant visual electrophysiological diagnostic exam, which can be used as a suitable objective measure of optic nerve function. The topic was greatly debated and many correlations between the magnitude of the VEP latency parameters and parameters of Humphrey static perimetry suggested that the abnormal cortex responses in patients with glaucomatous changes could be tested by both electrophysiological and physical methods. Moreover, the optic nerve glaucomatous damage observed by reduction in ganglion cell layer and retinal fibre layer thickness through SD-OCT tests, which are known to precede Humphrey visual field defects, correlates with VEP latency parameters, thus consolidating the position of the VEP testing in glaucoma progression. Keywords: glaucoma, visual evoked potentials, latency, optic nerve

Introduction Even today, glaucoma is considered an eye condition that can progress to major vision loss and blindness. Owing to its insidious onset and lack of symptoms, patients frequently come late at ophthalmology check-up. In some instances, optic nerve damage continues to progress despite adequate treatment and good intraocular pressure (IOP) control. According to data from the World Health Organization, the prevalence of glaucoma for the population of 40–80 years old is 3.54%. Prevalence rates of primary open angle glaucoma (POAG) was found higher in African population (4.20%), while the prevalence of primary angle closure glaucoma (PACG) is

highest in the Asian population (1.09%). In 2013, the number of people (ages between 40–80 years) who had glaucoma was estimated to be 64.3 million, numbers that are going to increase to 76.0 million in 2020 and the forecast by 2040 is to become close to 111.8 million [1]. Diagnosis of glaucoma is based on the IOP values, optic nerve head appearance (cupping of optic nerve) in fundus examination, visual field assessment (VFA) for typical glaucomatous field defects, gonioscopy and pachymetry, with invaluable data also from SD-OCT regarding retinal fiber layer thickness (RNFL) and ganglion cell layer thickness (GCC). Electrophysiology in glaucoma brings valued information through pattern ERG, which

DOI:10.22336/rjo.2020.4

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detects macular ganglion cell dysfunction and VEP for nerve fiber layer loss and can be of aid in the evaluation of “glaucoma suspects” with risk factors for glaucoma such as high levels IOP or optic nerve head changes, even before detectable loss trough visual field exam [2]. One advantage of the electrophysiological methods is the possibility of testing various processing stages of the visual paths separately, thus electroretinogram (ERG) reflecting the activity of different retinal layers while visual evoked potentials (VEP) represent a brain response to visual stimuli [3]. By measuring the change of electrical signal over the occipital cortex in response to light stimuli, a visual evoked potential (VEP) can be recorded. Studies have shown that abnormal VEPs correlate with a degree of optic nerve damage [4,5]. To be able to register VEPs, the EEG signal is augmented by repetitive stimulation and light-evoked changes are isolated from the basal EEG reading. A waveform has been identified in normal individuals, characterized by 2 positive and 2 negative waves that alternate. The VEP waveform typically contains a primary negative wave (N1), then a positive wave P1, also known as P100 for its usual location at 100 msec); second negative (N2) and second positive (P2) peaks follow (Fig. 1).

The amplitude of onset of each peak is measured. Delay in the onset of a peak is referred to as latency and reflects some level of injury of the visual pathway (Fig. 2).

The standard protocols used worldwide are: 1) Pattern-reversal VEPs; those are elicited by both large 1-degree (°) checkerboard stimuli as well as small 0.25° checks. 2) Pattern onset/ offset VEPs; determined by the same checks as (1). 3) Flash VEPs, which are determined by a flash (brief luminance increment) that subtends a visual field larger or equal with 20° [6]. The electrodes are placed as follows (Fig. 3): For standard VEP, one electrode is placed on the occipital scalp that corresponds to the visual cortex at O (the active electrode) and another electrode at F (reference electrode). Another electrode is affixed and connected to the ground. Commonly used ground electrode positions include the forehead and vertex (C). Other possibilities are earlobe (A1 or A2), mastoid or linked earlobes (Fig. 3A). International Society for Clinical Electrophysiology of Vision (ISCEV) recommends a minimum of three active electrodes; from those there is one electrode at Oz (midline electrode) while two are placed at O1 and O2 (lateral electrodes), for multi-channel VEP. The active electrodes (one midline and two lateral) should be referenced to Fz. In order to increase

Fig. 1 Flash VEP: an initial negative peak (N1) followed by a positive peak; second negative (N2) and second positive (P2) peaks follow, and so on

Fig. 2 Normal amplitude and latency of a wave in pattern VEP

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sensitivity to lateral asymmetries there is the possibility of placing additional electrodes at PO7 and PO8. Those are referred to Fz as well [7]. The positions of the lateral electrodes are illustrated in Fig. 3B.

This paper summarized many of the studies that contributed to the impact of the VEP as a measure of optic nerve fiber loss detection in early glaucoma. We also included the papers concerning VEPs utilization in clinical setting for the objective evaluation of visual field defects, especially those that are typical in glaucoma.

Pattern VEP and flash VEP There are two main theories in glaucoma mechanisms; in both the increase of IOP determines destruction of optic nerve fibers which results in the loss of visual function, associated with an alteration of the VEP waveforms. Because of these facts, many studies have followed the presence of a correlation between visual field defects and VEP parameters. So far we acknowledge that the VEP is overshadowed by the foveolar responses and thus reflects macular function, and when the parameters were altered it meant a modification of the central visual field [8]. The most used VEP stimulus is full- field pattern-reversal because

eyes are evaluated separately; it also focuses on the evaluation of the anterior segment of the visual pathways. For uncooperative patients the most used are flash VEP assesses the continuity of the visual pathways; compared to the than the pattern reversal type, the variability of its latencies has been noted [9]. A case-control study conducted by Jha et al. measured the VEP as a potential indicator of health status of retinal ganglion cells in POAG. Twenty POAG eyes were followed (group of patients aged 45 to 74 years, all of whom were on beta-blocker drops for IOP control). Another group of 40 individuals between 38 and 72 years old formed the control group, giving a control to case ratio of 2:1. Pattern reversal VEP (PR-VEP) and flash VEP have been assessed by monocular technique, with recordings taken of N75, P100, and N145. They found a significantly prolonged N145 latency in the patient group versus the control with the use of PR-VEP (P=0.011). N75 and P100 latency were prolonged, but not significantly versus the control. The amplitudes of PR-VEP have been significantly reduced in the patient group, while flash VEP had the opposite result of significantly higher amplitudes for the patient group. Compared to the control group, the latencies of flash VEP were not significantly prolonged. In comparing the 2 techniques, flash VEP recorded significantly prolonged latencies compared to PR-VEP. However, PR-VEP was found to elicit significantly higher amplitudes compared to flash VEP, and therefore was more reliable. They concluded that the deterioration in ophthalmic variables caused by POAG was reflected in increased latency and with a difference between the amplitude values of flash VEP versus PR-VEP. In another case-control study by Watts et al., a decrease of P1’s amplitude was correlated in Humphrey perimetry with the degree of visual field alteration. Flash VEP was used, allowing the analysis of patients with minimal distortion of the results due to opaque media, incorrect refraction, pupillary anomalies, and stimulus presentation. Two groups: first one (POAG group, mean age 66) comprising 74 patients (total 130 eyes) were compared with the second group (control group, mean age 66) of 125 patients (total 250 eyes).The most significant finding was that in the first group, the P1 amplitude was significantly reduced compared

Fig. 3 Electrode positions in standard and multi-channel VEP: 1A. Standard VEP electrodes location. The midline (Oz) electrode is active. The reference electrode is located at location Fz. The midline position is indicated by subscript z. 1B. Multi-channel VEP active electrodes exam locations PO7, PO8, O1, O2, (lateral electrodes) and Oz (midline electrode location)



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to the second group (P=0.001), but the difference was not significant for P2 amplitude measurements. There was also a negative correlation between reduction in P1 and the ratio of cup to disc vertical diameter (P=

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neuropathy due to glaucoma earlier and faster [16]. “Isolated-check” refers to a specific cell or pathway that can be assessed. This study enrolled patients in two groups: a POAG group with 25 patients and a control group with 20 healthy patients. The examination of the ganglion cell layer (GCC) was performed by OCT. Results of this study performed by Chen et al. on Neucodia visual electrophysiological diagnostic system (MKWH AMD, Huzhou Medconova Medical Technology, Inc.) suggested that icVEP has a similar diagnostic power to OCT measurements of GCC in early glaucoma detection if the comparison is realized using quantitative data [17]. Also, when using the icVEP for early POAG, it detected visual function anomalies in approximately 60% of the eyes with q specificity as high as 90% in a study by Fan et al. For Fan et al., Signal To Noise Ratio (SNR) correlated with both a RNFL thickness decrease and central visual field loss severity [18]. Multifocal VEP Multifocal VEP (mfVEP) was determined to be an effective investigation in the assessment of early glaucomatous changes in patients with unreliable or unconfirmed visual field modification. Graham SL et al have followed 436 consecutive cases (retrospective assessment) suggested as glaucoma suspects were followed within a year and mfVEP changes were correlated with disease progression stages and had an overall sensitivity of 97.5% in detecting glaucoma with established subjective field loss. The group with low-risk suspects had normal mfVEP in 92.2%. A subgroup was tested using masked disc assessment alone, and, in this group, mfVEP had a similar sensitivity in detecting anomaly in Humphrey perimetry measurements, but with a higher specificity (89.2% vs. 79.5%) [3]. Alterations of implicit times and amplitudes of N2 response in the central area might be superior in early glaucoma detection compared to Humphrey perimetry assessment in a study by Golemez et al. [19]. In a study of 126 eyes divided in 4 groups: 30 healthy, 28 glaucoma suspect, 48 early glaucoma and 20 advanced glaucoma cases with investigations performed every 3 months in a 6 months-period results showed that implicit times of all mfERG

components were significantly delayed in glaucoma, also both delayed implicit time and reduced amplitude of N2 wave in the central area are effective prognosticators in early POAG diagnosis [14,19]. Conclusion From the literature review, we can conclude that VEP is a valuable visual electrophysiological tool. It is useful for POAG patients for the evaluation of optic nerve defects. Unlike the visual field assessments, VEP has the crucial advantage of been completely objective, because the electrophysiological tests are a more unbiassed examination of the function of the optic pathway. This objectiveness is because cognitive factors (like tiredness, stress and others) or patient’s motor skills (especially for the elder patients) are absent. As the cited studies have shown, VEP modifications are significantly associated with optic nerve and visual field specific alterations, which make VEP method a powerful predictor of early POAG. Further, the relationship between VEP parameters and visual field MD forces the conclusion that physical methods and electrophysiological methods can be used in a complementary way. Also, the VEP latencies are significantly associated with MD, which raises the possibility that the retina-visual cortex transfer interruption determines the gravity of glaucomatous damage.

Acknowledgements All authors have equal contribution to the paper. Authors acknowledge the support of the POCU 2014-2020 “Diagnosticul si terapia bolilor rare sistemice cu afectare oculara – OCURARE”. References 1. Tham YC et al. Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040: A Systematic Review and Meta-Analysis. Ophthalmology. 2014; 121(11):2081-2090. 2. Robson AG et al. ISCEV guide to visual electrodiagnostic procedures. Documenta Ophthalmologica. 2018; 136(1):1-26. 3. Graham SL et al. Objective VEP perimetry in glaucoma: asymmetry analysis to identify early deficits. Journal of Glaucoma. 2000; 9(1):10-19.



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4. Watts M, Good P, O'neill E. The flash stimulated VEP in the diagnosis of glaucoma. Eye. 1989; 3(6):732-737. 5. Jha MK et al. Visual evoked potentials in primary open angle glaucoma. Journal of Neurodegenerative Diseases. 2017. 6. Mitchell JVOMB et al. ISCEV standard for clinical visual evoked potentials: (2016 update). 7. Odom JV et al. ISCEV standard for clinical visual evoked potentials: (2016 update). Doc Ophthalmol. 2016; 133(1):1-9. 8. Ermers H, De Heer L, Van Lith G. VECPs in patients with glaucoma. in XIth ISCERG Symposium. 1974. Springer. 9. Jha MK et al. Visual Evoked Potentials in Primary Open Angle Glaucoma. 2017. 10. Ruchi K et al. The potential use of pattern reversal visual evoked potential for detecting and monitoring open angle glaucoma. Current Neurobiology. 2012; 3(1):39-45. 11. Horn FK et al. Visual evoked potentials under luminance contrast and color contrast stimulation in glaucoma diagnosis. Journal of Glaucoma. 2000; 9(6):428-437. 12. Towle V et al. The visual evoked potential in glaucoma and ocular hypertension: effects of check size, field size, and stimulation rate. Investigative Ophthalmology & Visual Science. 1983; 24(2):175-183. 13. Parisi V. Impaired visual function in glaucoma. Clinical Neurophysiology. 2001; 112(2):351-358. 14. Fortune B et al. Comparing multifocal VEP and standard automated perimetry in high-risk ocular hypertension and early glaucoma. Investigative Ophthalmology & Visual Science. 2007; 48(3):1173-1180. 15. Greenstein VC et al. Visual evoked potential assessment of the effects of glaucoma on visual subsystems. Vision Research. 1998; 38(12):1901-1911. 16. Zemon V et al. Novel electrophysiological instrument for rapid and objective assessment of magnocellular deficits associated with glaucoma. Documenta Ophthalmologica. 2008; 117(3):233. 17. Chen X, Zhao Y. Diagnostic performance of isolated-check visual evoked potential versus retinal ganglion cell-inner plexiform layer analysis in early primary open-angle glaucoma. BMC Ophthalmology. 2017; 17(1):77. 18. Fan X et al. Applications of Isolated-Check Visual Evoked Potential in Early Stage of Open-Angle Glaucoma Patients. Chinese Medical Journal. 2018; 131(20):2439. 19. Gölemez H, Yıldırım N, Özer A. Is multifocal electroretinography an early predictor of glaucoma?. Documenta Ophthalmologica. 2016; 132(1):27-37.


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EMR in Eye Units Camburu Georgiana, Purcărea Victor Lorin “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Correspondence to: Georgiana Camburu, MD, PhD student, Assistant Professor, “Carol Davila” University of Medicine and Pharmacy, Bucharest, 37 Dionisie Lupu Street, Code 020021, Bucharest, Romania, Mobile phone: +40742 239 844, E-mail: [email protected] Accepted: December 4th, 2019

Abstract There are some questions that have to be asked when considering if EMR is suitable for a National Health System: First the Viability, Reliability, and Integrity of the EMR. When thinking about EMR, it has to be compounded based on some standards, that can be taken from other Health Systems or own. Secondly, the proper type of Ophthalmic EMC System (Web based EMR/ Client Server EMR) should be taken into consideration. Another question that raises is if EMR can not only be specialized in Ophthalmology, but also Subspecialties such as Glaucoma, Retina and other. This offers a possibility of completing a Database that can be used for Studies and Audit and improve the Health System. Using EMR can also offer accurate data that can estimate the prevalence of some specific conditions and rare diseases. Keywords: electronic medical record, electronic medical record in Eye Unit

Electronic Medical Record (EMR) is a systematized collection of patient health information that is electronically stored in digital formats [1]. Another definition was offered by the Institute of Medicine (US) Committee on Improving the Patient Record, but instead they used the term Computer-based patient record as an electronic patient record that resides in a system specifically designed to support users by providing access to complete and accurate data, alerts, reminders, clinical decision support systems, links to medical knowledge, and other aids [3]. Here, the term tries to offer a full picture of the whole process: collecting, entering and analyzing the data. The history of EMC started in the mid-1960s, when Lockheed developed an electronic system known then as the first clinical information system [2]. Previous to this, patients

kept all their health information (lab reports, visit notes, medications) on sheets of paper that were labeled using the patients’ names. There are some questions that have to be asked when considering if EMR is suitable for a National Health System: first the Viability, Reliability, and Integrity of the EMR. When thinking about EMR, it has to be compounded based on some standards that can be taken from other Health Systems or own. Secondly, the proper type of Ophthalmic EMC System (Web based EMR/ Client Server EMR) should be taken into consideration. Another question that raises is if EMR can not only be specialized in Ophthalmology, but also in Subspecialties such as Glaucoma, Retina and other. This offers a possibility of completing a database that can be used for studies and audit and improve the Health System. Using EMR can also offer accurate data that can estimate the

DOI:10.22336/rjo.2020.5

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prevalence of some specific conditions and rare diseases. When talking about Viability, Reliability and Integrity of the EMR, first it has to be decided if it is part of a hospital informational system, with both functions: clinical and administrative or medical information system, just collecting, storing, and making available the data important for the patient care. The aim of this type of system is not that of facilitating financial information, but instead focusing on improving patient care [3]. As a system, the viability of the EMR depends on the Operational effectiveness - having those resources needed for accurate patients’ records, Financial effectiveness - trying to maximize the income and to reduce the loss of resources, Compliance - ensuring the function of the system based on laws and regulations. The quality of the system is often missed or ignored in medical practices. The quality of EMR can be measured by the Integrity and Reliability of the system. A reliable EMR should provide the right information to the right user at the right moment. The EMR should offer both the physician and the patient the information desired. Reliability is related to Integrity. Some records can be illicitly modified to maximize the income for a procedure that cost less or never happened. Integrity of the system means that the data is stored without missing records, multiple records of the same event, records that contain incorrect information or events that never happened [4]. Integrity is based on Standards The Certification Commission for Healthcare Information Technology is a federal nonprofit government contractor that certifies EMR systems. The Certification is offered after evaluating the functionality, security and interoperability, or the capacity of the systems to communicate with one another and incorporate digital imaging in the patient record. The Eye Care Working Group, funded by AAO, is a group of clinicians, users, vendors, researchers, that stipulates the Digital Imaging and Communications in Medicine (DICOM) Standards for Eye practice [5].

Next, the type of EMR System we want to use has to be chosen. By choosing Application Service Provider Web based EMR, the data is stored online, so the information cannot be freely accessed at any moment in time, being controlled by the provider. Moreover, the provider can update the soft or use the data stored without consent. Other limitations are the necessity of an internet connection, slow performance during the peak times during the day, or slow downloads. Client Server EMR system has high performances. The user does not need an Internet Connection, so it has high speed. The disadvantage is the low interoperability between systems with different software losing precious data. Recently, another type of system appeared, fulfilling the previous systems limitations. By using locally hosted or Hybrid option EMR, the user can have both the software and access the data whenever needed. Nevertheless, the user has to purchase his own server and connect to it via Internet, when outside of the office [6]. Further, EMRs have not only been designed particularly for Eye care, but also for subspecialties. This type of EMR can be suitable for a Department or Sub-specialized Clinic. Using EMR in Pediatric Ophthalmology is a challenge because it combines the particularities found in Ophthalmology, heavy use of imaging and documentation, and also Paediatric particularities as changes that occur in developmental stages. In a survey undergone to reveal the benefit of routine EMR used by paediatric ophthalmic clinicians, participants had to choose from a list of 18 benefits. The mean was 8.59/ per participant. The limitation previously mentioned can explain the low usage of EMR in the ophthalmic paediatric field [7]. Novack analyzed the data gathered from the patients who have suffered retinal detachment provided by EMR. The conclusion was that only 41% of the hospitals in the US have electronically available medical information from outside providers or sources when treating a patient, physicians in outpatient settings far worse, only 14% of the office-based physician sharing data with providers outside their organization [8]. Reisman offers an explanation to this result, referring to the lack of standards among different ERH vendors. Clinicians can store and analyze previous measurements, for

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example Central Corneal Thickness, when needed. One of the pros. of using EMRs is that they provide a rich database, from where the user is able to reach some conclusion and improve the medical care. A study undergone by N. Restrepo showed that the user is able to extract Primary Open Angle Glaucoma from EMR for genetic associations. In other words, he created an algorithm that can extract a specific clinical subtype of glaucoma from EMRs in the absence of digital photographs [9]. Gignac illustrated the Contribution of EMR to the management of rare diseases. His conclusion was that the use of specific EMR might improve surveillance of rare diseases and sharing of data between centers will support clinical research and innovation [10]. In order to choose the applicability of EMR, a metanalysis can be performed on some studies undergone in the health systems from different countries. In a study made in the US about long term financial and clinical impact of EHR on Academic Ophthalmology Practice it appeared that the difference in inflation did not change significantly before and 9 years after the EHR implementation [11]. Another study about the use of EHR and administrative data for public health surveillance of the eye health and vision related conditions in the US showed that EHR can offer additional information to make “a comprehensive vision” and eye health surveillance with both disadvantages and advantages [12]. The cross-sectional study about the distribution and extent of EMR in eye units across UK suggested that it is pleasing to see numerous eye units that are using EMR (45.3% currently using, 26.4% implementing), but the concept still needs further optimization for the records system to allow proper data transfer between units. To eliminate some of these differences, the Royal Collage of Ophthalmologists defined a minimum of standards indicated for the vendors as “a must”. Another aspect that can be reflected on is the satisfaction of the user/ system members in managing EHR, which in our case, is the physician or the patient. A descriptive qualitative study that entailed the physician’s satisfaction with EMR in health centers from Al Ain United Arab highlighted that the physicians are satisfied

with EMR and have a good perception about it [13]. In a pilot study regarding the amount of time the ophthalmologists using EHR spend examining the patient and correlated with the patient’s satisfaction, demonstrated that even if the ophthalmologist spent one-third of time looking at the computer, the patient satisfaction levels were very high. Conclusion Our opinion is that the implementation of the EMR is the National Health System is a fundamental step in the progression and optimization of the Eye Care. References 1. Gunter TD, Terry NP. The emergence of national electronic health record architectures in the United States and Australia: models, costs, and questions. J Med Internet Res. 2005; 7(1):e3. 2. https://www.elationhealth.com/clinical-ehr-blog/history-ehrs/. 3. Dick RS, Steen EB, Detmer DE. Institute of Medicine (US) Committee on Improving the Patient Record, 1997, National Academies Press (US), Washington (DC). 4. Rechtman Y, Rashbaum K, Gelzer R. Understanding Electronic Medical Records, Reliability and Integrity as Critical Components of Medical Practice Valuation, Profitability, and Compliance. The CPA Journal. The Voice of the Profession. June 2019. https://www.cpajournal.com/2019/07/15/understanding-electronic-medical-records/. 5. Brown K, Lum F, Noecker R, Rich WL, Solomon K. Viability of ophthalmic electronic medical records hinges on interoperability. Ocular Surgery News. U.S. Edition. July 25 2009. 6. Wendy W, Lee A. Comparison of Ophthalmic Electronic Medical Record Systems. Ophthalmology web. June 29 2011. https://www.ophthalmologyweb.com/Tech-Spotlights/26584-A-Comparison-of-Ophthalmic-Electronic-Medical-Record-Systems/. 7. Cross MS. Electronic Medical Records in paediatric ophthalmology: A study of potential users and uses to inform design. 2018/05/28. https://discovery.ucl.ac.uk/id/eprint/10049547. 8. Novack GD, Lim MC. Retinal Detachment: Patient Perspective and Electronic Health Records. American Journal of Ophthalmology. December 2019; 208:64-67. 9. Restrepo NA, Farber-Eger E, Goodloe R, Haines JL, Crawford DC. Extracting Primary Open-Angle Glaucoma from Electronic Medical Records for Genetic Association Studies. June 10 2015. https://doi.org/10.1371/journal.pone.0127817. 10. Bremond-Gignac D, Lewandowski E, Copin H. Contribution of Electronic Medical Records to the



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Management of Rare Diseases. BioMed Research International. 2015; 1-4. https://doi.org/10.1155/2015/954283. 11. Michele CL, Roma PP, Lee VS, Weeks PD, Barber MK, Watnik MR. The Long-Term Financial and Clinical Impact of an Electronic Health Record on an Academic Ophthalmology Practice. J Ophthalmol. 2015; 329819. doi: 10.1155/2015/329819. 12. Davidson A, Lum F, Chiang MF, Saaddine JB, Zhang X, Crews JE, Chou CF. Use of Electronic Health Records and Administrative Data for Public Health Surveillance of Eye Health and Vision-Related Conditions in the United States. American Journal of Ophthalmology. December 2012; 154(6 Suppl):S63-70. doi: 10.1016/j.ajo.2011.10.002. 13. Al Alawi S, Al Dhaheri A, Al Baloushi D et al. Physician user satisfaction with an electronic medical records system in primary healthcare centres in Al Ain: a qualitative study. BMJ Open. 2014; 4:e005569. doi: 10.1136/bmjopen-2014-005569.


REVIEW


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Is Central Corneal Thickness a reliable independent factor in decision-making regarding the management of

patients with high IOP? Camburu Georgiana, Zemba Mihail, Purcărea Victor Lorin “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Correspondence to: Georgiana Camburu, MD, PhD Student, Assistant Professor, “Carol Davila” University of Medicine and Pharmacy, Bucharest, 37 Dionisie Lupu Street, Code 020021, Bucharest, Romania, Mobile phone: +40742 239 844 E-mail: [email protected]

Accepted: November 8th, 2019

Abstract As time passes, we discover that things that were supposedly considered to be well known are in fact not as they seemed. Maybe the process is like this because we try to simplify our daily practice, but by doing so, don’t we tend to trespass the whole picture? However, what happens if these factors affect our decision-making? Clinicians should incorporate CCT into the thinking process and should not focus on “corrected IOPs”, because, besides CCT, there are many factors of corneal biomechanics that affect IOP. Keywords: Central Corneal Thickness, GAT IOP, adjusted IOP

As time passes, we discover that things that were supposedly considered to be well known, are in fact not as they seemed. Maybe the process is like this because we try to simplify our daily practice, but by doing so, don’t we tend to trespass the whole picture? However, what happens if these factors have an impact on our decision-making? CCT has been considered a useful tool in measuring IOP for long time. Various formulas were made to adjust IOP. It is advised that normal CCT is 550 microns. If so, why is Goldmann Applanation Tonometer (GAT) considered the Gold Standard [1] and why can it give accurate results, even if it does not take into consideration CCT? The Goldmann device was invented in 1950 [2] and is a tonometer described by the Imbert-Fick principle [3]. In an ideal sphere with dry thin walls, the internal pressure is equal with the

force divided by the area of the flattening. Goldman stated that using a 3.06 mm diameter, the resistance of the cornea [3] during the flattening is compensated by the tear film meniscus capillary attraction [4,5]. Because many clinicians were measuring the CCT during every examination mainly to adjust the IOP that was taken by using GAT, The American Academy of Ophthalmology conducted a study which revealed that the use of CCT in adjusting IOP did not predict POAG. The report stated clearly that CCT still remains a significant component of complete ocular examination, as an independent predictive factor for POAG [6]. In a study made by Brandt et al., a re-analysis of the OHTS evaluated the prediction developing of POAG. They compared the prediction accuracy of POAG for un/ adjusted IOP with five different formulas [5]. After examining the data of 1433 participants, the

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conclusion was that for calculating the risk of developing POAG in patients with ocular hypertension is accurate to use IOP and CCT obtained and not to apply correction formulas [5]. After reviewing the results of Brandts et al., Dr. Medeiros suggested that instead of using IOP formulas, clinicians should better incorporate risk information as provided, and regarding the legitimacy of that CCT as a true independent glaucoma risk factor, he considered that further investigations are required [5]. In a study that aimed to evaluate if CCT could be a useful tool for the disease progression prognostic in ocular hypertensives, the author recommended that measuring CCT is advisable when the clinical finding does not correlate with the IOP token by the applanation technique [7]. Dr. Elliot Kirsten conducted a study trying to determine the validity of Ehler monogram in adjusting GAT IOPs. Ehlers monogram is widely used. He reveled that using the monogram in correcting the error made by omission of the CCT will increase the error instead of decreasing it [8]. In the article entitled “Corneal thickness: It's time we all get rid of the correction factor from the glaucoma equation”, Dr. Al Busadi stated that clinicians should incorporate CCT into the thinking process and should not focus on “corrected IOPs”, because there are many factors, besides CCT, that have an impact on IOP such as: corneal hydration, connective tissue composition, and bio elasticity [8]. In fact, there are other biomechanical proprieties of the cornea that can affect IOP. Luce [9] was the first to introduce the term “Corneal Hysteresis” as an indicator of corneal biomechanics. Congdon [10] stated a lower Hysteresis, and not CCT, associating progression of visual fields defects of glaucoma patients. Is Corneal Hysteresis a more reliable factor? Dr. Pillai believes that CCT correction formulas provide less accurate IOP values and, since the cornea and the optic nerve are continuous structures, she considers that corneal hysteresis can be corelated with the ability of the optic nerve to tolerate intraocular pressure [11].

Should GAT IOP measurements be corrected taking into consideration the corneal biomechanics properties? Two hundred eighty-nine patients were subjected to IOP measurements using both PDCT and GAT. PDCT asserts that the IOP obtained is independent of the corneal properties. This study [12] conducted by dr. Park showed that there was a weak correlation between PDCT and GAT, and worse for GAT CCT adjusted, in patients with considered thick cornea. They suggested that adjusting GAT IOP in patients with increased corneal thickness may underestimate IOP, having as a result a delaying in starting the treatment [13]. A possible explanation was offered in the article entitled “Data do not support adjusting tonometry for central corneal thickness”. The author stated that “CCT is an important component of error in Goldmann, but it is almost certain that other factors, such as the viscoelastic properties of the cornea, minimize the influence of central corneal thickness on tonometry [14,16]. Dr. Ahmed Elshiekh, University of Dundee, Scotland, affirmed that GAT is difficult to correct and is affected by corneal stiffness [14], compound of thickness, curvature and biomechanical properties of the corneal tissue. A correction just for thickness is inadequate because it represents an incomplete approach. All the parameters were evaluated individually, but there is no guidance on how to combine these effects, as “they are all at play at the same time” [8]. …so, which is the best approach? CCT should be measured every 5 years because the value also decreases in time. Moreover, there are other factors that affect CCT measurements, such as prostaglandins, topical dorzolamide, topical beta-blockers, estrogen levels during ovulation and pregnancy, diabetes [15,17]. Dr. Steven R. Sarkisian Jr. takes into account the pressure and CCT and states that unless CCT is > 600 µm or < 500 µm, it does not let it affect his assessment [13,18].

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A conclusion of Dr. Adam Reynolds is that we cannot build an accurate algorithm in adjusting IOP based on CCT, because IOP measurements have a high le

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