Symposium on Drugs 1 1 1

RETINAL DETACHMENTS AND TOPICAL OCULAR MIOTICS

HAROLD BEASLEY, MD FORT WORTH, TEXAS

FREDERICK T. FRAUNFELDER, MD PORTLAND, OREGON

There is increasing suspicion that topical ocular miotic therapy in selected persons may precipitate retinal detach­ments. This is a rare event and prob­ably does not occur in patients free of retinal pathology. Data supporting a possible cause and effect relationship, obtained from the National Registry of Drug-Induced Ocular Side Effects, a survey of the Retina Society, medico­legal decisions, and a review of the literature, is presented.

THERE have been about 100 cases of possible miotic-related retinal detachments reported in the litera­ture. 1-9 Many of the cases implicate miotic therapy in precipitating a retinal detachment even though the detachment occurred months after initiation of topical ocular miotic therapy. These cases are question­able as to a cause and effect rela­tionship. There are, however, many dramatic reports of patients either started on miotic theIiapy or receiv­ing increased dosage& of the miotic a few hours before liIymptoms oc­curred. Histories include a sudden

Submitted for publication Oct 22, 1978.

From the Department of Ophthalmology, Univer· sity of Oregon Health Sciences Center, Portland (Dr Fraunfelder).

Presented at the 1978 Annual Meeting of the American Academy of Ophthalmology, Kansas City, Mo, Oct 22·26.

Reprint requests to 1212 W Presidio, Fort Worth, TX 76102 (Dr Beasley).

95

onset of floaters, light flashes, and subsequent discovery of a retinal detachment. Certainly, the patient assumes a cause and effect relation­ship. The packet insert for echothi­ophate states, "should be used with great caution, if at all, where there is a history of retinal detachments"lO; however, few other miotics carry such a warning.

This report reviews the data on miotics and possible retinal detach­ments based on ophthalmologists' reports in the National Registry of Possible Drug-Induced Ocular Side Effects. Also, if miotics do precipi­tate retinal detachments, it is likely that retinal surgeons have some impression about a possible cause and effect relationship and the fre­quency of such occurrences. For this. reason, the members of the Retina Society were polled. At­tempts were also made to find medi­colegal precidence as to what is currently being determined in the court of law concerning miotics and retinal complications. Possibly, based on these sources and the literature, current guidelines for the clinician could be established.

Over the past two years there have been 36 cases of possible mi­otic-induced retinal detachments re­ported to the Registry. Data in

96 BEASLEY AND FRAUNFELDER OPHTH AAO

these retrospective reports are sketchy. In general, detachments have occurred with any topical ocular miotic, almost always in pa­tients with preexisting retinal or retinovitreal pathologic conditions. The shortest intervals for a retinal detachment to occur after starting miotic therapy appear to be in aphakic eyes. The time from the start of medication to the begin­ning of retinal symptoms has been as short as an hour and as long as a few weeks.

One hundred and twenty-four members of the Retina Society were sent a questionnaire to which 91 replied. Seventy-two members, or approximately 80%, felt miotics were a probable factor in causing some detachments, 18 did not think there was an association, and one had no opinion. Those members answering affirmatively reported approximately 480 retinal detach­ment cases in which miotics prob­ably played a role. There were 35 retinal surgeons who reported 1 to 5 cases, 22 who reported 6 to 10 cases, 6 who reported 11 to 20 cases, and 5 who reported more than 20 retinal detachment cases in their practices that were probably drug related. Response to this ques­tionnaire indicates that most ret­inal surgeons believe there is a relationship between the use of miotics and the occurrence of a retinal detachment. While all mio­tics were implicated, pilocarpine and phospholine iodide, probably because of their more common use, were the most frequently mentioned.

Litigation is a fact of life, and we are familiar with a number of cases of miotic retinal detachment se­quences for which some legal settle­ment was made. Bettmanll cites

three patients, all of whom had a predisposition to detachments with either lattice degeneration or my­opia. In each instance the detach­ment occurred within a few weeks after starting or increasing miotic solution. He points out that this complication did not indicate mal­practice. However, legal problems arose because the patients were not seen for a long period of time, were not informed of the possibility of a drug-related event, or were not told what symptoms after miotic use should cause alarm.H

There were two cases with litiga­tion in which one of us (H.B.) was consulted at the request of the drug company involved. The first case was a middle-aged man with my­opia and elevated ocular pressure. He was treated with 3% pilocarpine OU for one month, but this proved inadequate and was increased to 5% pilocarpine. Floaters developed in the left eye within a few days after starting the 3% pilocarpine, and a field defect developed shortly after 5% pilocarpine was started. A vitreous hemorrhage, a large horse­shoe tear, and a retinal detach­ment were found OS. Detachment surgery was unsuccessful because of massive vitreous retraction.

The second case was a middle­aged woman with myopia and open-angle glaucoma who was started on 1% pilocarpine OU. Within 24 hours there were visual symptoms caused by a vitreous hemorrhage. Examination revealed horseshoe tears in the upper tem­poral quadrant OD and the upper nasal quadrant OS. The areas were surgically treated without compli­cation. It is difficult to prove or disprove that these retinal findings were caused by miotics, but equivo­cation is not acceptable from a

VOLUME 86 JANUARY 1979 SYMPOSIUM ON DRUGS 97

legal standpoint. No doubt many cases of what appears to be a mi­otic-related event are mere coinci­dence. However, both of our cases were settled out of court with the legal comment that a definitive causal relationship was not estab­lished, but that the circumstances and temporal relationship aroused suspicion.

From a physiologic and pharma­cologic standpoint, it is certainly possible for miotics to cause retinal tears and detachments. It has been demonstrated that the ora serrata and the underlying choroid move forward with accommodation.12

Moses13 showed that the ora moved forward about 0.05 mm for each diopter of accommodation. Ultra­sonograms have shown that the posterior surface of the lens moves forward in accommodation with in­stillation of 2% pilocarpine.14-16 This dynamic activity may disturb the anterior vitreous, which could be transmitted to abnormal vitreo­retinal attachments.17 This mecha­nism of pull is more likely to be affected in abnormal vitreoretinal attachments than normal ones.

Lemcke and Pischel6 suggested anatomic features that might be common to detachments caused by miotics. These are characterized by limited detachments with one or more relatively small holes. This finding has not been confirmed in other studies or reports. Whether or not miotics can cause retinal de­tachments may always be conjec­tural, since the studies to prove this in the human, while not only costly to fund, might have difficulty being passed by a human research com~ mittee.

Based on current knowledge, the clinician should consider several

points before prescribing miotic drugs. There are numerous cases reported that suggest that a topical ocular miotic may have precipitated a retinal detachment. Since these cases were almost always in abnor­mal or diseased eyes, it is likely that a preexisting retinal or retino­vitreal pathologic condition was present before the use of miotics. Because of what is known about the physiologic and pharmacologic effects of this group of drugs on the eye, it is possible that a miotic could precipitate a detachment. Be­fore a patient is treated with a miotic, the pupils should be dilated so that the central and peripheral retinas can be examined.

The patient who has a higher frequency of retinal detachment than the normal population, ie, retinovitreal pathology, high my­opia, or previous retinal detach­ment, should be told of retinal de­tachment symptoms and the slight risk of using miotic therapy. Since litigation in medical circles is in­creasing, the ophthalmologist must be aware of his responsibilities in keeping his patients informed of reasonable risks. Drug companies should include package inserts ex­plaining that miotics should be used with caution and that, in some patients, their products may have the potential to precipitate retinal detachments.

In summary, while there is no positive cause and effect relation­ship between miotics and retinal detachments, there is, in a selected population, a strong suspicion. While the ophthalmologist may be slow to accept this incomplete data, he must realize that the court of law has not supported the conservative approach to this possible drug-re­lated event.

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REFERENCES

1. Leber T: Die Krakheiten der Netzhaut und der Schnerven, in Handbuch der Ge­sammten. Augenheilkunde Leipzig, Breit­kopf & Hartel, 1877.

2. Freilich DB, Seelenfreund MH: Miotic drugs, glaucoma and retinal detachment. Mod Prob Ophthalmol 15:315-318, 1975.

3. Ackerman AL: Retinal detachments and miotic therapy, in Pruett RL, Regan CDJ (eds): Retinal Congress, New York, Appleton-Century-Crofts, Inc, 1972, pp 533-539.

4. Kraushar MF, Podell DL: Miotic-in­duced retinal detachment, in Pruett RL, Regan CDJ (eds): Retinal Congress, New York, Appleton-Century-Crofts, Inc, 1972, pp 541-545.

5. Mortimer CB: Retinal detachment. Appl Ther 12:23-26, 1970.

6. Lemcke HH, Pischel DK: Retinal de­tachments after the use of phospholine iodide. Trans Pac Coast Otoophthalmol Soc 47:157, 1966.

7. LaRocca V: Retinal detachment from di-isopropyl fiuorophosphate in an aphakic eye. NY State J Med 52:1329-1331, 1952.

8. Gradle HS, Snydacker D: Retinal de­tachment occurring in primary compensated glaucoma. Am J Ophthalmol 23:52-59, 1940.

9. Pape LG, Forbes M: Retinal detach­ment and miotic therapy. Am J Ophthalmol 85:558-566, 1978.

10. Physicians'Desk Reference-For Oph­thalmology. Oradell, NJ, Litton Industries Inc, 1978, p 78.

11. Bettman JW Sr: Ophthalmology, the Art, the Law, and a Bit of Science. Birming­ham, Ala, Aesculapius Publishing Co, 1977, pp 151-152.

12. Schepens CL, Bahn GC: Examination of the ora serrata: Its importance in retinal detachment. Arch Ophthalmol 44:677-690, 1950.

13. Adler FH: Adler's physiology of the eye, ed 2. St Louis, CV Mosby Co, 1953, p 359.

14. Coleman DJ: Unified model for accom­modative mechanism. Am J Ophthalmol 69:1063-1079, 1970.

15. Abramson DH, Coleman DJ, Forbes M, et al: Pilocarpine: Effect on the anterior chamber and lens thickness. Arch Ophthal­mol 87:615-620, 1972.

16. Abramson DH, Franzen LA, Coleman DJ: Pilocarpine in the presbyope. Arch Oph­thalmol 89:100-105, 1973.

17. Hogan MJ: The vitreous, its structure, and relation to the ciliary body and retina. Invest Ophthalmol 2:418-445, 1963.