Cystoid macular oedema associated with brimonidine therapy

Clinical and Experimental Ophthalmology

2003;

31

: 159–166

Letters to the Editor

_______________________________

Letters to the Editor

Clinical Case Notes

Fungal granuloma following ruthenium plaque radiotherapy of a choroidal melanoma

We describe an episcleral fungal granuloma in a 91-year-oldwoman, masquerading as extrascleral extension of a choroidalmelanoma previously treated with Ruthenium

106

plaque radio-therapy. To our knowledge this is the first reported case of its type.

C

ASE

R

EPORT

A 91-year-old woman presented in May 1999 with a 6-monthhistory of gradual deterioration of vision in her left eye. She wasbilaterally pseudophakic following cataract surgery 20 years previ-ously. Her physical state was poor due to advanced Parkinson’sdisease.

Her best-corrected visual acuity was 6/12 in the right eye, andcount fingers in the left eye. The anterior segments of both eyesand her right fundus were normal. Fundoscopy of the left eyerevealed a 10-mm diameter pigmented, elevated choroidal lesionwith lipofuscin, involving her left macula. Photography was notpossible because of the presence of a small pupil with an iris cliplens. The tumour had an ultrasound appearance consistent with achoroidal malignant melanoma with a height of 3.5 mm and a baseof 6.9

×

9.3 mm (Fig. 1). There was no evidence of metastases onchest X-ray or liver ultrasound. Following discussion with thepatient and her family, a 20-mm notched Ruthenium

106

plaque wasinserted in May 1999 for local tumour control.

Examination over the subsequent 6 months showed signs ofearly regression of the tumour. In early March 2000, 10 monthsfollowing surgery, the area underneath and around the tumourappeared swollen and indented and a small amount of surroundingsubretinal fluid was present. The eye remained quiet with noanterior or posterior segment inflammation and no signs suggestiveof orbital or intraocular infection. Ultrasound suggested anincrease in size of the tumour with a height of 7 mm and a base of20

×

20 mm (Fig. 2). There was evidence of a small associatedretinal detachment and an area of reduced scleral and episcleralreflectivity suggesting extrascleral extension.

In view of her advanced age, the patient and her family declineda MRI scan, which was offered for more accurate imaging ofpossible extrascleral extension of the choroidal melanoma. Theyopted for immediate enucleation as a means for local tumourcontrol, and this was performed within 1 week.

Histopathology revealed a mixed cell choroidal malignantmelanoma, 8 mm in maximum dimension, arising close to theorigin of the optic nerve (Fig. 3). There was focal breach of Bruch’smembrane and limited scleral spread, but no evidence of vascularinvasion. The surgical margins were free of tumour with no evi-dence of extrascleral spread or optic nerve involvement. A large

fungal granuloma centred on the posterior episclera beneath thetumour was seen. This comprised septate, branched fungal hyphaeresembling a

Fusarium

or

Aspergillus

spp. (Fig. 4), and surroundingneutrophils, foamy histiocytes, epithelioid cells and foreign bodytype giant cells. Fungal culture was not possible because of histo-pathological tissue fixation. Although there were no hyphae notedin the sclera, the granulomatous inflammation extended throughsclera and into choroid, causing a serous retinal detachment over-lying the tumour. The histological picture of a fungal granulomawas responsible for the clinical and ultrasonographic appearanceseen prior to enucleation.

Given the indolent history of the granuloma, its completeexcision at enucleation, and the patient’s poor systemic health,treatment with systemic antifungals was considered unwarrantedand fortunately has not been necessary to date. The patient hasremained free of orbital recurrence of the melanoma and of fungalorbital infection.

D

ISCUSSION

Malignant melanoma of the choroid is the most common primaryintraocular neoplasm in adults. The goal of radiotherapy is todestroy all viable tumour and prevent local and systemic relapse. Itoffers an eye and vision-sparing alternative to enucleation, andeffective local control in over 90% of cases.

1

Fungi cause a wide spectrum of infections in the eye and orbit.Postoperative fungal infections in immunocompetent hosts ofteninvolve filamentous species such as

Aspergillus

and

Fusarium

. Mostreported cases involve fungal keratitis or endophthalmitis follow-ing cataract surgery.

2

Iatrogenically induced fungal scleritis hasbeen reported after pterygium removal, strabismus surgery, scleralbuckling, trabeculectomy and cataract extraction.

2–4

Iatrogenicfungal conjunctivitis after subconjunctival injection with yeast-contaminated saline has also been described.

5

Fungal scleritis is arecognized occurrence after postoperative radiotherapy of pterygiawith subsequent scleral radionecrosis.

6–8

It is believed that scleralulceration, ischaemic tissues, an altered precorneal tear film, cal-cific plaques and minor epithelial breaches interact to create anenvironment in which surface contamination may lead to infection.To our knowledge this is the first reported case of an episcleralfungal granuloma at the site of a radiotherapy plaque for choroidalmalignant melanoma.

The location of the granuloma in our case suggests intraopera-tive spore implantation and subsequent growth. Fungal conidia arecommon airborne particles and inhabit the nose and paranasalsinuses of healthy hosts. They are also part of the microbialconjunctival flora.

5

Perioperative contamination of the plaquecarrier, cotton buds, marking dye or irrigation fluids are otherpossible sources of local infection. Both alcohol disinfection andthe radiation reduce the bioburden on a radioactive plaque, butsteam sterilization (121

°

C for 15 min) is necessary to ensure total

160 Letters to the Editor

microbial destruction. The plaque in our case had been soaked andcleaned with ethanol, but our radiation physicists were concernedwith the risk of leakage of Ruthenium

106

with repeated autoclaving.A variety of factors may potentiate fungal growth. The use of

topical corticosteroids and antibiotics has been associated withlocal fungal disease, probably through reduced local immunity anda change in the bacterial flora.

5

Significant scleral and episcleralradionecrosis and ischaemia is unlikely to be present less than1 year after radiotherapy, but should be considered in the aetio-logy. General debilitation may have played a role in our case inview of the patient’s advanced age and Parkinson’s disease,although her systemic medications did not include immune modu-lating agents.

Our case demonstrates several differences between exogenousfungal and bacterial ocular infections. A latency of weeks tomonths between implantation and clinical disease is common infungal disease compared with a much shorter period for bacterialinfection. Fungal disease tends to be more localized, often present-

ing as an abscess. Ocular discomfort is generally less severe withoften no external sign of fungal infection.

3

In radionecrosis-associated fungal scleritis, a delay in diagnosis was found to beuniversal and in several cases the infection mimicked a serousretinal detachment or pseudotumour.

7

The ability of fungal infec-tions to masquerade as ocular tumours is well recognized, and inour case the episcleral granuloma and associated scleral inflam-mation gave an ultrasonographic appearance suggesting enlarge-ment and extrascleral spread of the previously treated melanoma.Magnetic resonance imaging has proven useful in orbital fungalinfections (

Aspergillosis and Mucormycosis

) but unfortunately this wasdeclined by the patient and her family.

Figure 1.

Ultrasound showing the choroidal melanoma, withhighly reflective anterior border and low internal reflectivity.

Figure 2.

Ultrasonographic evidence of recurrent choroidalmelanoma with an area of reduced scleral and episcleral reflectivitysuggestive of extrascleral extension.

Figure 3.

Low power haematoxylin and eosin stain of the choro-idal melanoma, whose cells show abundant cytoplasmic melanin,with an overlying serous retinal detachment. Underlying this isseen part of a large abscess, centred in episclera, and consisting ofnumerous inflammatory cells that extend through sclera intochoroid.

Figure 4.

High power methanamine silver stain showing fungalhyphae.

Letters to the Editor 161

In summary, we described an episcleral fungal granuloma in a91-year-old woman, masquerading as extrascleral extension of achoroidal melanoma previously treated with Ruthenium plaqueradiotherapy. The unusual clinical presentation and possible aetio-logy of the infection are discussed.

Salim Okera

MB BS(Hons)

,

1

Tom Dodd

FRCPA

,

2

DineshSelva

FRANZCO

1

and James Muecke

FRANZCO

1

1

Department of Ophthalmology, Royal Adelaide Hospital, and

2

Department of Tissue Pathology, Institute of Medical andVeterinary Sciences,

Adelaide, South Australia, Australia

R

EFERENCES

1. Finger PT. Radiation therapy for choroidal melanoma.

SurvOphthamol

1997;

42

: 215–31.2. Theodore FH. Etiology and diagnosis of fungal postoperative

endophthalmitis.

Ophthalmology

1978;

85

: 327–40.3. Klotz SA, Penn CC, Negvesky GJ, Butrus SI. Fungal and

parasitic infections of the eye.

Clin Microbiol Rev

2000;

13

:662–85.

4. Jager MJ, Chodosh J, Huang AJW, Alfonso AC, Culbertson WW,Forster RK.

Aspergillus niger

as an unusual cause of scleritis andendophthalmitis.

Br J Ophthalmol

1994;

78

: 584–6.5. Behrens Baumann W. Mycoses of the anterior segment of the

eye. In: Behrens Baumann W, ed.

Developments in Ophthalmology

,Vol. 32. Madgeburg: Karger, 1999.

6. Moriarty AP, Crawford GJ, McAllister IL, Constable IJ. Severecorneoscleral infection: a complication of beta irradiationscleral necrosis following pterygium excision.

Arch Ophthalmol

1993;

111

: 947–51.7. Kumar B, Crawford GJ, Morlet GC. Scedosporium prolificans

corneoscleritis: a successful outcome.

Aust NZ J Ophthalmol

1997;

25

: 169–71.8. Huang FC, Huang SP, Tseng SH. Management of infectious

scleritis after pterygium excision.

Cornea

2000;

19

: 34–9.

Letter to the Editor

Acute vitreomacular traction with early spontaneous resolution

We report a case of acute vitreomacular traction with spontaneousposterior vitreous detachment, documented by optical coherencetomography (OCT). Resolution of symptoms occurred 1 weekafter presentation.

C

ASE

R

EPORT

A 46-year-old Chinese man who had no significant past medical orsurgical history presented with a day’s history of acute metamor-phopsia in his left eye. There was no history of trauma, surgery,floaters, flashes of light, micropsia, dyschromatopsia or recentstress. There was no history of ingestion of corticosteroids. Best-corrected Snellen visual acuity was 6/12 in his right eye and 6/18in his left eye. Slit-lamp examination of the anterior segment wasnormal.

Dilated fundal examination revealed normal retina in his righteye; however, the left fundus showed serous elevation of themacula in a ‘tent’ shaped configuration with obliteration of thefoveal depression. There was no evidence of exudative or haemor-rhagic change (Fig. 1). Contact lens biomicroscopy showed thepresence of posterior cortical vitreous adherent to the anteriorretinal surface, with the fovea being pulled upwards in the config-uration of a cone. There were no retinal tears or lesions in theperipheral retina. Vitreomacular traction was clearly demonstratedon B-scan ultrasound (Fig. 2). Fundal fluorescein angiography(FFA) was unremarkable.

Figure 1.

Left fundus showing serous elevation of the macula in a‘tent’ shaped configuration with obliteration of the foveal depression.

Figure 2.

B-scan ultrasound of the left eye demonstrating vitreo-macular traction.


A week later, the patient developed spontaneous posteriorvitreous detachment with resolution of symptoms. His visual acuityreturned to 6/9 in the left eye. Fundoscopy showed the presence ofa posterior vitreous detachment with flattening of the ‘tent’ shapedconfiguration. A linear horizontal tomogram was obtained throughfixation with the Optical Coherence Tomography Scanner (ZeissHumphrey Systems, Dublin, CA, USA; use kindly arranged by theDefence Medical Research Institute, Singapore). The reflectivelayer anterior to the neurosensory retina was consistent with thatof the posterior hyaloid face (Fig. 3). The posterior hyaloid,although detached from the fovea, was still attached to the opticdisc. There was loss of normal foveal contour with an area ofsubfoveal hyporeflectivity suggestive of a foveal cyst or fovealdetachment.

D

ISCUSSION

Vitreomacular traction syndrome is defined as a distinct clinicalsyndrome caused by vitreous traction or adhesions on the maculausually because of an incomplete posterior vitreous detachment orseparation.

1,2

Typically, the patient presents with acute centralvisual loss and is associated with metamorphopsia, monoculardiplopia, photopsia or micropsia. Visual acuity at presentationranges from 6/12 to 6/200 (median 6/60).

1

Clinical examinationreveals partial posterior vitreous detachment with persistent

anteroposterior traction. Other associated signs include dumbbell-shaped zone of cortical vitreous remaining attached to the maculaand optic nerve head, subtle areas of traction retinal detachment,cystic macular change, retinal striae, thickened posterior hyaloidface, epiretinal membrane and tractional changes on the opticnerve head.

1,2

The clinical recognition of vitreomacular traction syndromerequires a high index of suspicion. Although there are severalimportant causes of submacular detachment, several featuresfavoured the diagnosis of vitreomacular traction in this case:history of acute central visual disturbance, lack of subretinal bloodor elevated lesions, conical or ‘tent’ shaped configuration to themacula, presence of cystoid spaces in the neural retina, and incom-plete separation of the posterior hyaloid from the retinal surface.An epiretinal membrane was not clinically visible. Normal fundusfluorescein angiography excluded central serous chorioretinopathyand choroidal neovascularization.

The rapidity of spontaneous resolution in our patient wasunusual. Most reported cases of spontaneous posterior vitreousseparation occurred between 6 weeks and 15 months after presen-tation.

3–5

Hikichi

et al.

described in their series that 11% of patientswith vitreomacular traction developed complete posterior vitreousdetachment in 6–32 months and that these separations couldresolve cystoid changes and improve or maintain the visual acuity.

3

In the present case separation of the posterior vitreous hadoccurred within 1 week of onset of symptoms, precluding docu-mentation of foveal traction by the vitreous on OCT. The OCTscan was obtained 1 day after the resolution of symptoms. The lossof normal foveal contours and appearance of a foveal cyst on OCTmaybe compared to findings seen in stage I macular hole. Wepostulate that the detachment of the posterior vitreous may haveaborted a progression towards a full thickness macular hole. Therapid resolution also allowed complete recovery of symptoms,hence preventing chronic changes to the fovea such as persistentcystoid macular oedema, which would affect visual acuity. Ourpatient declined further follow-up visits after resolution of hissymptoms. As such we were unable to obtain later OCT images ofthe patient.

Smiddy

et al.

described electron microscopy of vitrectomyspecimens where fibrous astrocytes were the predominant cell typeand no retinal pigment epithelium cells could be observed.

6

Theseastrocytes were stimulated by traction from a partially detachedvitreous and entered through discontinuity or small breaks in theinternal limiting membrane.

6

Pre-existing cell migration onto theretina may cause an area of firm posterior vitreomacular adhesionand prevent completion of a posterior vitreous detachment.

1,5

Hikichi

et al.

studied the course of the disease in 53 patientsover 60 months where the median age of patients was 66 years.

3

They observed that cystoid changes in the neurosensory retina ofthe macula were present in 43 (81%) of 53 eyes with accompany-ing macular traction. Even in patients without cystoid changes atthe time of diagnosis, many develop changes later in life and suchchanges tended to persist. The degree of vitreous traction on themacula is thought to influence developing cystoid oedema andthese changes cause a drop in visual acuity. Symptoms may worsenbecause traction causes retinal vascular incompetence, leakage, andcystoid changes.

Smiddy

et al.

studied 16 eyes with vitreomacular traction thatunderwent pars plana vitrectomy to release vitreoretinal tractionon the macula.

7

Sixty-three per cent of these patients had improve-ment of at least 2 lines and all had subjective improvement of

Figure 3.

Optical coherence tomography of the left eye showingposterior vitreous detachment.


symptoms. Patients with better preoperative visual acuities demon-strated better postoperative visual acuities. Our patient, whostarted with a visual acuity of 6/18, improved to 6/9 uponseparation of the posterior cortical vitreous from the foveaspontaneously.

Optical coherence tomography was first used as a tool in thediagnosis of vitreomacular traction by Sulkes

et al.

4

as it can clearlydefine the vitreoretinal interface. Focal or multifocal vitreomaculartraction can be easily identified and OCT has been shown to bemore sensitive than biomicroscopy in identifying vitreomacularadhesions.

5

Due to the rapidity of onset and resolution of vitreo-macular traction in our patient, we only managed to obtain OCTimages showing posterior vitreous detachment from the fovea.Although the early post-resolution OCT images of our patientshowed an area of subfoveal hyporeflectivity, it is possible thatwith time, these changes would resolve in the absence of persistentvitreous traction.

In summary, diagnosis of vitreomacular traction requires a highindex of suspicion. Fluorescein angiography and B-scan ultrasoundare useful tools in diagnosis; in addition, OCT is a new tool thatcan be used to confirm the diagnosis. Spontaneous resolution ofthe vitreomacular traction can occur early as demonstrated in thiscase.

Ching-Li Cheng

FRCS(Ed)

, Sek-Tien Hoh

FRCS(Ed)

,Jacob Cheng Yen Chuan

MB BS

, Edmund Yick-Mun Wong

FRCS(Ed)

and Adrian Hock-Chuan Koh

FRCS(Ed)

Singapore National Eye Centre and Singapore Eye Research Institute,Singapore

R

EFERENCES

1. Smiddy WE, Michels RG, Green WR. Morphology, pathol-ogy, and surgery of idiopathic vitreoretinal macular disorders.A review.

Retina

1990;

10

: 288–96.2. McDonald HR, Johnson RN, Schatz H. Surgical results in

the vitreomacular traction syndrome.

Ophthalmology

1994;

101

: 1397–402.3. Hikichi T, Yoshida A, Trempe CL. Course of vitreomacular

traction syndrome.

Am J Ophthalmol

1995;

119

: 55–61.4. Sulkes DJ, Ip MS, Baumal CR, Wu HK, Puliafito CA. Sponta-

neous resolution of vitreomacular traction documented byoptical coherence tomography.

Arch Ophthalmol

2000;

118

:286–7.

5. Gallemore RP, Jumper JM, McCuen BW, Jaffe GJ, Postel EA,Toth CA. Diagnosis of vitreoretinal adhesions in maculardisease with optical coherence tomography.

Retina

2000;

20

:115–20.

6. Smiddy WE, Green WR, Michels RG, de la Cruz Z.Ultrastructural studies of vitreomacular traction syndrome.

AmJ Ophthalmol

1989;

107

: 177–85.7. Smiddy WE, Michels RG, Glaser BM, de Bustros S. Vitrec-

tomy for macular traction caused by incomplete vitreousseparation.

Arch Ophthalmol

1988;

106

: 624–8.


Idiopathic polypoidal choroidal vasculopathy as a cause of a disciform macular scar

Idiopathic polypoidal choroidal vasculopathy (IPCV) is a vascularabnormality of the inner choroid with a network of branchingvessels of variable dimensions terminating in aneurysmal likeenlargements with episodic serosanguinous detachments of theretinal pigment epithelium and neurosensory retina.

1–3

The natural course of IPCV is characterized by recurrentpigment epithelial detachments, with resolution of the exudativeand haemorrhagic manifestations usually.

4

We report a case ofIPCV that lead to a disciform scar at the macula, with correspond-ing poor vision.

C

ASE

R

EPORT

A 65-year-old Chinese woman first presented in December 1996complaining of blurring of vision in her right eye for a duration of4 months. She did not have a history of high myopia or angiodstreaks. She did not have any history of systemic disease.

Her Snellen visual acuity in that eye was 6/24; this did notimprove with the aid of a pinhole and with refraction. The best-corrected visual acuity in the contralateral left eye was 6/12.Examination of her anterior segments was unremarkable except forthe presence of mild nuclear sclerotic cataracts in both eyes con-sistent with her age.

Dilated fundoscopic examination of the right eye showed thepresence of a pigment epithelial detachment (PED) centred roundthe fovea measuring approximately 3

×

3 disc diameters. Therewere no soft drusen or pigment changes consistent with age-relatedmacular degeneration.

Fundoscopic examination of the left eye showed a few harddrusen just temporal to the fovea. No soft drusen were detected.

Fundus fluorescein angiography showed the presence of a hyper-fluorescent lesion consistent with the presence of a pigment epithe-lium detachment, as well as the presence of a staining defectinferonasally (Fig. 1a). No hyperfluorescence was detected at thenotch of the PED, which could potentially be treated with the laser.

Indocyanine green angiography showed the presence of somemore prominent choroidal vasculature inferonasally as well assuperotemporally, with the presence of aneurysmal like lesionssuperotemporally (Fig. 1b). However, these were not noted at thetime; thus no treatment was considered.

The patient’s vision remained fairly stable over the subsequentyear but the patient defaulted follow up thereafter.

When she presented again in September 2000, the best-corrected vision in the right eye had deteriorated from 6/24 at thelast follow up 3 years ago to counting fingers at 0.5 m.

Examination showed that a disciform scar had formed over thefovea corresponding to the position of the pigment epithelialdefect that was detected 4 years previously (Fig. 2). At this time,IPCV had become commonly diagnosed in our patients, and theoriginal indocyanine green angiogram from 1996 was reviewed.The polypoidal lesions were then noted, with one of the polypscorresponding to the position of the notch of the original pigmentepithelium detachment.

Therefore, in retrospect, this patient’s pigment epitheliumdetachment was secondary to IPCV.


D

ISCUSSION

This patient presented with a pigment epithelial detachment inDecember 1996. The most likely condition was, and still is, age-related macular degeneration. The search, back in 1996, was forany treatable subretinal neovascular membrane (especially with thepresentation of a notched pigment epithelial detachment). As aresult, a fundal fluorescein angiogram was performed. Indocyaninegreen angiography had at that time just been introduced and itwas thus performed, but unfortunately, the condition of IPCV wasmissed initially. The differential diagnoses of a pigment epithelial

detachment also included central serous choroidopathy, hyper-tensive choroidopathy, metastasis and choroidal tumours.

5

Thepatient was 61 years old at that time, hence age-related maculardisease was considered as the most likely cause then.

Although IPCV had been described as early as 1990 by Yan-nuzzi

et al.

1

up until 1996, this condition had not been as widelyrecognizable as it is today. As such, IPCV was overlooked in theinitial work up of this patient.

The patient returned 4 years later after defaulting follow up andby then, the disciform macular scar that we were seeing was theend stage of the natural progression of her condition. Fortuitously,in the light of our experience that IPCV is more prevalent in ourpopulation than previously thought (the presence of IPCV inAsians has been reported, especially in Japanese patients

6

), wereviewed the fluorescein and indocyanine green angiograms of thepatient again and detected the presence of a polypoidal lesion onindocyanine green angiography that corresponded to the positionof the notch in the PED. Indeed, based on the data from anotherstudy by Yannuzzi

et al.

,

7

with a series of 167 patients, IPCV shouldbe suspected in an elderly patient with an exudative maculopathy,especially when the patient is non-white and has few or no drusenin the fellow eye of a unilateral case. Yannuzzi

et al.

have alsosuggested that in Asians, ‘IPCV may masquerade as neovascular-ized AMD’.

3

The differential diagnoses of a disciform macular scar includeage-related macular degeneration, angiod streaks, high myopia ortrauma. However, the absence of drusen or focal hyperpigmenta-tion in that eye and the angiographic confirmation of the absenceof any subretinal neovascular membrane exclude the possibility ofage-related macular degeneration in our patient. The clinical fea-tures of the patient also exclude angiod streaks, high myopia andtrauma as likely causes for the disciform scar.

At the same time, the indocyanine green angiogram showedconclusively the presence of numerous aneurysmal choroidallesions, with one polyp corresponding to the position of the notch.

Figure 1.

(a) Fundal fluorescein angiogram showing notchedpigment epithelial detachment. (b) Indocyanine green angiographywith arrow pointing to polyp.

Figure 2.

Fundus photograph showing disciform scar at the macula.


It is important to make this diagnosis of IPCV as the conditionis treatable. Laser treatment of IPCV has been reported to bepresumptive, empirical and anecdotal, but rational.

1,3

Photocoagu-lation of the leaking polypoidal lesions, which present as focalintense hyperfluorescence with late indocyanine green staining,has been associated with dramatic resolution of the serosanguinouscomplications and restoration of vision in the uncontrolled seriesof patients of Yannuzzi

et al

.7 The high success rate in the treat-ment, with low recurrence, could be attributed to the pathology ofIPCV being a slow flow system without neovascular drive.8

The point worth emphasizing in this case is that over the periodof 4 years, the lesion evolved into a disciform scar, without treat-ment. Unlike age-related macular degeneration, fibrovascular disci-form scarring is reported as unusual in IPCV.8 With the benefit ofthe indocyanine green angiogram performed 4 years ago, we areable to demonstrate that IPCV sometimes evolves naturally into adisciform lesion. Hence the detection of a disciform lesion mightnot just indicate the possibility of age-related macular degenera-tion but that of IPCV as well.

In our patient, this diagnosis will also impact on the manage-ment and prognosis for the second better-seeing eye.

We also want to highlight the unusually bad outcome of thiscase as a result of its progression to a disciform macular scar. Itshows that the natural history of IPCV can be poor when theexudates in the PED fail to resolve spontaneously and instead resultin disciform scarring.

Chin Tek Chuah FRCS(Ed) (Ophth)1 andCaroline Chee FRCOphth2

1Singapore National Eye Centre and2Department of Ophthalmology, National University Hospital,

Singapore

REFERENCES

1. Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathicpolypoidal choroidal vasculopathy. Retina 1990; 10: 1–8.

2. Spaide RF, Yannuzzi LA, Slakter JS, Sorenson JA, Orlock DA.Indocyanine green angiography of idiopthic choroidal vascu-lopathy. Retina 1995; 15: 100–10.

3. Yannuzzi LA, Ciadella A, Spaide RF et al. The expandingclinical spectrum of idiopathic polypoidal choroidal vasculo-pathy. Arch Ophthalmol 1997; 115: 478–85.

4. Schneider U, Gelisken F, Kressig I. Indocyanine green angio-graphy and idiopathic polypoidal choroidal vasculopathy. Br JOphthalmol 1998; 82: 98–9.

5. Gass JD, Norton EW, Justice J. Serous detachment of theretinal pigment epithelium. Trans Am Acad Ophthalmol Otolaryn-gol 1966; 70: 990–1015.

6. Uyama M, Matsubara T, Fukushima I et al. Idiopathic poly-poidal choroidal vasculopathy in Japanese patients. Arch Oph-thalmol 1999; 117: 1035–42.

7. Yannuzzi LA, Wong D, Sforzolini BS et al. Polypoidal choroi-dal vasculopathy and neovascularised age-related maculardegeneration. Arch Ophthalmol 1999; 117: 1503–10.

8. Ahuja RM, Stanga PE, Vingerling JR, Reck AC, Bird AC.Polypoidal choroidal vasculopathy in exudative and haemor-rhagic pigment epithelial detachments. Br J Ophthalmol 2000;84: 479–84.


Cystoid macular oedema associated with brimonidine therapy

Brimonidine tartrate 0.2% is a new selective α2-adrenergic agonistthat has recently been approved for long-term treatment of raisedintraocular pressure due to open angle glaucoma or ocular hyper-tension. Brimonidine lowers intraocular pressure by a dual mode ofaction through reduction of aqueous humour production andenhancing uveoscleral outflow.

A number of adverse effects associated with brimonidinetherapy have been described and include dry mouth, eye redness,stinging/burning, drowsiness, blurred vision, conjunctival folliclesand ocular allergy.

We report a case of cystoid macular oedema (CMO) in apatient associated with the use of brimonidine tartrate 0.2% eyedrops. The CMO resolved after discontinuation of brimonidine,both clinically and angiographically.

CASE REPORT

A 74-year-old Caucasian woman presented in March 1994 with acataract in the right eye. She had undergone an uncomplicated leftintracapsular cataract extraction with no intraocular lens implant in1984. Examination showed no capsular remnant or vitreous in theanterior chamber. Her visual acuity was 6/9 in the right eye and6/6 in the left. Intraocular pressure was 16 mmHg in the right eyeand 14 mmHg in the left. Ophthalmological examination revealedan aphakic left eye with a cup-to-disc ratio of 0.7 compared to 0.4in the right eye.

In July 1994, routine uncomplicated phacoemulsification cata-ract surgery with intraocular lens implant was performed in theright eye. Postoperative best-corrected visual acuity was 6/6.

The patient was reviewed regularly and her intraocular pressurewas noted to increase in the left eye from 16 mmHg in 1994 to24 mmHg in 1998. Visual field testing showed a slowly progressivesuperior arcuate scotoma in this eye. Treatment with topicaltimolol 0.5% was commenced in the left eye in January 1998.

She experienced adverse reactions to timolol consisting ofnightmares and migraine-like headaches and it was substituted withlatanoprost nocte in March 1998. Intraocular pressure decreasedfrom 24 mmHg to 21 mmHg over a 2-week period. Dorzolamidetwice a day and brimonidine twice a day was added to this regimenin April 1998, to further reduce intraocular pressure.

Her intraocular pressure finally decreased to 12 mmHg anddorzolamide was ceased in June 1998. Visual acuity for the periodto June 1998 remained stable at 6/6 as did the visual fields. She wasmaintained on latanoprost and brimonidine at this stage. Intraocu-lar pressure was 14 mmHg in the left eye.

In December 1998, she presented to one of the authors (SL)with a 2-week history of conjunctival injection and reduced visionin the left eye. Best-corrected visual acuity was 6/18. Examinationshowed follicular conjunctivitis, clear cornea and absence of iritis.Dilated fundoscopy suggested presence of CMO. Her IOPremained low at 15 mmHg on the left. There was no other macularpathology such as epiretinal membrane, branch retinal vein occlu-sion or juxtafoveal telangiectasia to account for the macularoedema. Fluorescein angiography confirmed an area of hyperfluo-rescence suggestive of CMO (Fig. 1). Examination of the right eyewas unremarkable.


As brimonidine has been associated with follicular conjuncti-vitis, it was deemed to be the cause of the patient’s problems.Brimonidine was subsequently ceased with improvement in CMOangiographically; visual acuity also improved to 6/9 10 days later(Fig. 2). This coincided with resolution of the follicular conjuncti-vitis. Follow-up examinations and fluorescein angiography showedresolution of CMO over a 6-month period.

During this period, a trial of medical treatment with acetazola-mide (250 mg t.d.s. for 3 weeks) enabled improvement of visualacuity from 6/9 to premorbid acuity of 6/6. The intraocular pres-sure was 18 mmHg in June 1999.

The patient has remained on treatment with latanoprost to datewithout any recurrence of CMO.

DISCUSSION

A number of ophthalmic preparations including latanoprost (prosta-glandin analogue),1 betaxolol (beta-adrenergic receptor blocker)2

and dipivefrin hydrochloride (adrenergic agonist)3 have beenreported to be associated with CMO.

To our knowledge, the association between CMO and use ofbrimonidine has not been reported. It is important to note thatlatanoprost was continued after brimonidine was ceased as mono-therapy to control intraocular pressure. It was felt that brimonidinewas the cause of our patient’s follicular conjunctivitis and con-current CMO. Both these clinical entities showed marked resolu-tion upon cessation of brimonidine therapy.

It has been well recognized that topical epinephrine therapymay induce CMO. Kramer found that in aphakic eyes the concen-tration of epinephrine reaching the choroid and retina was higherthan in phakic eyes.4 In aphakic patients, brimonidine may alsoreach the macula in higher concentrations. A rebound hyperaemiaphenomenon has been described with the use of dipivefrin and thiswas proposed as a possible mechanism for the development of

CMO. Kolker and Becker also described alterations in capillarypermeability induced by topical epinephrine therapy.5 Epinephrinehas activity at both α- and β-receptors and the precise role of thesereceptors in the development of CMO is still unknown. Further-more, brimonidine is a selective α2-agonist. This observationsuggests that α-receptor activity may play a role in drug-inducedCMO.

Although there are other causes of CMO, which include epi-retinal membrane, branch macular retinal vein occlusion, juxta-foveal telangiectasia and uveitis, this patient did not exhibit any ofthese features.

It is important that clinicians recognize CMO as a possiblecomplication of brimonidine therapy, particularly in aphakic eyes.

Peter Kim MB BS(Hons) andSomsak Lertsumitkul FRANZCO

Department of Ophthalmology, Liverpool Hospital, Sydney,NSW, Australia

REFERENCES

1. Rowe JA, Hattenhauer MG, Herman DC. Adverse side-effectsassociated with latanoprost. Am J Ophthalmol 1997; 124:683–5.

2. Hesse RJ, Swan JL 2nd. Aphakic cystoid macular edema sec-ondary to betaxolol therapy. Ophthal Surg 1998; 19: 562–4.

3. Mehelas TJ, Kollarits CR, Martin WG. Cystoid macularedema presumably induced by diprivefrin hydrochloride(Propine). Am J Ophthalmol 1982; 94: 682.

4. Kramer SG. Epinephrine distribution after topical administra-tion to phakic and aphakic eyes. Trans Am Ophthalmol Soc 1980;78: 947.

5. Kolker AE, Becker B. Epinephrine maculopathy. Arch Ophthal-mol 1968; 79: 552–62.

Figure 1. Left eye at presentation. Fluorescein angiogram show-ing marked cystoid macular oedema.

Figure 2. Left eye at 10 days follow up. Fluorescein angiogramshowing partial resolution of cystoid macular oedema.

Documents

Cystoid macular oedema associated with brimonidine therapy