- Email: [email protected]
Pharmacologic Therapy of Aphakic and Pseudophakic Cystoid Macular Edema
Pharmacologic Therapy of Aphakic and Pseudophakic Cystoid Macular Edema 1985 Update LEE M. JAMPOL, MD
Ab$tract: Major advances in the pharmacologic therapy of aphakic cystoid macular edema (ACME) have not occurred since 1982. Topical nonsteroidal anti-inflammatory agents are still not commercially available for ocular therapy. Topical indomethacin remains the one agent which has been proven to be of prophylactic value for angiographic aphakic cystoid macular edema although other non-steroidal agents may also work. The therapeutic value of these compounds for established ACME remains uncertain. No prospective randomized prophylactic or therapeutic trials of either topical or systemic corticosteroids have been performed. [Key words: Aphakic cystoid macular edema, corticosteroids, indomethacin, prophylaxis, prostaglandins.] Ophthalmology 92:807-810, 1985
In 1982, I reviewed the pharmacologic therapy of aphakic cystoid macular edema (ACME). I The following points were made: 1. Prospective masked randomized clinical trials are necessary to evaluate prophylaxis or therapy because of the highly variable clinical course. 2. The incidence of angiographic ACME is much greater than clinically significant macular edema. The small number of patients with clinically significant cystoid macular edema makes studies of this condition difficult. Studies of angiographic ACME mayor may not be relevant to clinically significant cystoid macular edema. 3. Topical and probably systemic indomethacin decrease the incidence of angiographic ACME but a sustained effect beyond one year or an effect on visual acuity has not been demonstrated. From the Northwestem University Medical School, Chicago. Presented at the Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 11-15, 1984. Reprint requests to Lee M. Jampol, MD, 303 E. Chicago Avenue, Chicago, IL 60(311.
4. No pharmacologic agent has been demonstrated to be of proven value for the therapy of established ACME. 5. Theoretical considerations suggest a possible additive effect of corticosteroids and non-steroidal antiinflammatory agents (such as indomethacin). The purpose of this paper is to update the current state of knowledge in regard to pharmacologic prophylaxis and therapy of ACME. .
TOPICAL NONSTEROIDAL ANTIINFLAMMATORY AGENTS To date (March 1985), no topical nonsteroidal antiinflammatory drug for ophthalmology has been approved by the Federal Drug Administration. Clinical trials with investigational protocols have continued with at least three different nonsteroidal anti-inflammatory agents}-IO Topical indomethacin continues to be a favorite medication in studies of aphakic ACME (Tables 1, 2). Both aqueous suspensions and oil-based solutions have been utilized. Topical flurbiprofen has recently been used as an anti-inflammatory agent for corneal and anterior 807
OPHTHALMOLOGY
•
JUNE 1985 •
VOLUME 92
•
NUMBER 6
Table 1. Pharmacologic Prophylaxis of Aphakic CME (Studies since last review') Investigator
Route
Duration and Dosage
Suprofen (0.5%, 1%)
Datiles et al 2
Topical
qid for 70 days
Yes
Indomethacin (1%)
Hollwich et all
Topical
qid for 3 months
Yes
Indomethacin (1%)
Urner-Bloch 6
Topical
qid for 12 weeks
Yes
Indomethacin (1%)
Yamaaki et al 3
Topical
tid for 4 weeks
Uncertain
Agent
Randomized
Result Trend toward reduced CME at 4 and 10 weeks Decreased CME 8-10 weeks postop Decreased CME 6 and 12 weeks postop Trend toward reduced CME 6-9 weeks postop
Comment Numbers too small; results not statistically significant No effect on visual acuity Numbers too small; results not statistically significant
CME = cystoid macular edema; qid = four times daily; tid = three times daily.
segment inflammation in animals and patients. 5 It has also been tested to determine its effect upon the pressure rise following argon laser trabeculoplasty.4 Some antiinflaI11matory effect has been demonstrated. To my knowledge, flurbiprofen has not been utilized in studies of aphakic ACME. An additional topical non-steroidal agent, suprofen, lias recently been tested for the prophylaxis of pseudophakic cystoid macular edema2 (see below).
SYSTEMIC NONSTEROIDAL ANTIINFLAMMATORY AGENTS An ever increasing spectrum of nonsteroidal antiinflammatory agents that inhibit prostaglandin synthesis is being utilized in medicine. The presently available agents have recently been reviewed. I I Systemic toxicity IS a common finding with many of these drugs. The most extreme example of this is benoxaprofen, a highly effective nonsteroidal anti-inflammatory drug that has been removed from the market because of hepatic and renal toxicity. Side effects of other nonsteroidal agents are commonly seen. PreVious trials in ophthalmology have also accentuated side effects of systemic indomethacin.12 Although in selected cases systemic nonsteroidal anti-inflammatory agents may be required, an effective topical formulation is more desirable.
RECENT CLINICAL TRIALS PROPHYLAXIS OF ACME
Several additional clinical trials have confirmed previous observations that topical indomethacin is effective in the prophylaxis of angiographic ACME (Table 1)03,6,7 The number of patients in these trials is small and the study design is less rigorous than previously reported trials. I In some studies, the number of patients is so small that only a trend has been seen that is not statistically significant. 3 There is no reason to question the previous conclusion that the incidence of angiographic ACME is decreased by the prophylactic administration of topical indomethacin. Additional trials in this area are not indicated. It is still true that an effect on visual acuity or even a sustained effect on ACME (beyond 1 year) has never been demonstrated. Datiles and associates have reported a prophylactic trial of a new topical prostaglandin synthesis inhibitor, suprofen.2 This agent facilitates mydriasis during the ca4tract surgical procedure. A trend towards a diminished incidence of angiographic ACME was seen in this study four and ten weeks after surgery (with the application of either 0.5% or 1% suprofen). The number of patients in this study was very small and the results were not statistically significant.
Table 2. Pharmacologic Therapy of Aphakic CystOid Macular Edema (ACME) (Studies since last review') Agent
Investigator
Route
Indomethacin (1%)
Cohen and Yannuzzi8
Topical
Combination of prednisolone acetate (1%) and indomethacin (1%) Indomethacin (1%)
Yannuzzi, Leibo, Sisc08
Miyake9
808
Duration and Dosage
Randomized
Result
Comment
Yes
"Near significant" effect on ACME
Study not yet reported in detail
Topical
1 month, frequency not reported Not described
No
80% of patients experienced visual improvement
50% relapses; Study not reported in detail
Topical
Not described
No
7 cases "responded " to indomethacin
Anecdotal
JAMPOL
•
CYSTOID MACULAR EDEMA
Unfortunately, no recent clinical trials have addressed value of topical, periocular, or systemic corticosteroIds for the prophylaxis of ACME. It has, however, been shown that topical corticosteroids and indomethacin prevent breakdown of the blood-aqueous barrier after cataract surgery, as measured by fluorophotometry.13 th~
OTHER CLINICAL STUDIES ON PROSTAGLANDINS AND ACME
THERAPY OF ESTABLISHED ACME
Miyake has measured prostaglandins in the aqueous humor of aphakic eyes in patients with vitreous incar• 16 ceratlOn. He showed elevated values. These values decreased following vitrectomy. Miyake iO has also shown that the incidence of angiographic CME in patients ut;tdergoing retinal detachment surgery can be diminished WIth the prophylactic use of indomethacin.
S~nce m~ last c~rtlcosterOids or
review, no therapeutic trials involving non-steroidal agents have been reported WIth the exception of brief notes by Yannuzzi8 and Miyake9 (Table 2). Yannuzzi mentions two clinical trials. In a randomized study utilizing topical indomethacin for the therapy of established ACME a "near significant effect" was mentioned. However, the details of this report have not appeared and we do not know if impr~ved vis~al acuity or decreased clinical or angiographIC cystOid macular edema was the end point. Yannuzzi also briefly mentions an uncontrolled trial of a combination of 1% prednisolone and 1% indomethacin for the therapy of established ACME. This was a consecutive series that was not randomized. The authors reported that 80% of the patients showed visual improvement. A high relapse rate was noted and an "on and off" effect of therapy was seen in many patients. Unfortunately, the fact that this study was not controlled makes interpretation of the results difficult. Miyake9 also describes patients with established ACME who have responded to topical indomethacin. Again, an "on and off" phenomenon with frequent relapses was seen. A similar effect was previously reported with topical fenoprofen. 14
ADDITIONAL STUDIES OF TOPICAL NONSTEROIDAL AGENTS Using fluorophotometry, Kraff and Sanders have shown that the combination of topical corticosteroids and indomethacin was more effective in reducing breakdown of the blood-aqueous barrier following cataract surgery than either topical indomethacin or topical corticosteroids alone. 13 In addition, each of these agents alone was more effective than placebo. Although one cannot necessarily extrapolate from fluorophotometric measurements to the presence of cystoid macular edema this study adds logical support to the supposition that ~ cO?lbination of corticosteroids and nonsteroidal agents mIght be more effective for either prophylaxis or therapy of ACME. Yamaaki and associates in a small trial suggested an association between leakage on iris angiography and the presence of ACME. 3 This is not surprising in view of the presence of breakdown of the blood-ocular barriers in both situations. Indomethacin was effective in diminishing the increased iris leakage and there was a trend towards a beneficial effect on angiographic cystoid macular edema in this study. Cunha-Vaz 15 has also suggested an association between breakdown of the blood-ocular barriers and ACME.
OTHER MEDIATORS OF CYSTOID MACULAR EDEMA It is possible that ACME may be partially mediated by other substances besides prostaglandins. 17 Other "~andi?ates" include neuropeptides (eg. substance P), hlstamme, and the kinins. Recent studies suggest that the miosis seen with inflammation or eye trauma may be mediated by substance p.17,18 However, breakdown of t~e blood-ocular barriers (at least the blood-aqueous bam:r) seems r;nore resistant to this peptide. No highly effectlve nontOXIC substance P antagonist exists at present. Arachidonic acid can be converted by lipoxygenases to other eicosanoids, including the leukotrienes. 17 Any role of these substances in cystoid macular edema is h~g~ly speculative. Effective nontoxic lipoxygenase inhIbItors would be helpful to study this possibility.
OTHER APPROACHES TO ACME Surgical therapy for aphakic cystoid macular edema remains a possibility especially in eyes with vitreous incarceration in the wound. Fung has reported a favorable effect of surgical vitrectomy on ACME in a randomized prospective controlled trial. 19 YAG laser vitreolysis may be similarly effective in such eyes although to date only uncontrolled trials have been reported?O,21 Randomized trials of this therapy are necessary. Kraff and associates have reported a possible role of post-operative ultraviolet light exposure in the development of angiographic ACME.22 Filtering UV light with a chromophore in the intraocular lens reduced the angiographic incidence of ACME. No effect on visual acuity was seen. The effect of near ultraviolet radiation on ACME could be mediated by generation of free radicals,23 which are known to facilitate the synthesis of prostaglandins or other mediators. The possible import~nc.e of this pathway in the development of visually sIgmficant ACME remains uncertain, and the long-term safety of the ultraviolet filtering chromophores available presently requires further studies.
ACKNOWLEDGMENT David Shoch, MD assisted with the translation of references 6 and 7.
809
OPHTHALMOLOGY
•
JUNE 1985 •
REFERENCES 1. Jampol LM. Pharmacologic therapy of aphakic cystoid macular edema; a review. Ophthalmology 1982; 89:891-7. 2. Datiles MB, Stark WJ, Fagadau WR, et al. Pseudophakic CME: clinical trial of a new topical prostaglandin synthesis inhibitor. Ophthalmology, In Press. 3. Yamaaki H, Hendrikse F, Deutman AF. Iris angiography after cataract extraction and the effect of indomethacin eyedrops. Ophthalmologica 1984; 188:82-6. 4. Hotchkiss ML, Robin AL, Pollack IP, Quigley HA. Nonsteroidal antiinflammatory agents after argon laser trabeculoplasty; a trial with flurbiprofen and indomethacin. Ophthalmology 1984; 91 :969-74. 5. Hurvitz LM, Spaeth GL, Zakhour I, et al. A comparison of the effect of flurbiprofen, dexamethasone, and placebo on cyclocryotherapyinduced inflammation. Ophthalmic Surg 1984; 15:394-9. 6. Urner-Bloch U. Pravention des zystoiden Makulaodems nach Kataraktextraktion durch lokale Indomethacin Applikation. Klin Monatsbl Augenheilkd 1983; 183:479-84. 7. Hollwich F, Jacobi K, Kuchle H-J, et al. Zur Prophylaxe des zystoiden Makulaodems mit Indometacin-Augentropfen. Klin Monatsbl Augenheilkd 1983; 183:477-8. 8. Yannuzzi LA. A perspective on the treatment of aphakic cystoid macular edema. Surv Ophthalmol 1984; 28:540-53. 9. Miyake K. Indomethacin in the treatment of postoperative cystoid macular edema. Surv Ophthalmol 1984; 28:554-68. 10. Miyake K, Miyake Y, Maekubo K, et al. Incidence of cystoid macular edema after retinal detachment surgery and the use of topical indomethacin. Am J Ophthalmol 1983; 95:451-6. 11. Jampol LM. Nonsteroidal anti-inflammatory drugs. Focal Points: Clinical Modules for Ophthalmologists 1984; Module 3.
P1n
VOLUME 92
•
NUMBER 6
12. Klein RM, Katzin HM, Yannuzzi LA. The effect of indomethacin pretreatment on aphakic cystoid macular edema. Am J Ophthalmol 1979; 87:487-9. 13. Sanders DR, Kraff M. Steroidal and nonsteroidal anti-inflammatory agents; effect on postsurgical inflammation and blood-aqueous humor barrier breakdown. Arch Ophthalmol 1984; 102:1453-6. 14. Burnett J, Tessler H, Isenberg S, Tso MOM. Double-masked trial of fenoprofen sodium: treatment of chronic aphakic cystoid macular edema. Ophthalmic Surg 1983; 14:150-2. 15. Cunha-Vaz JG, Travassos A. Breakdown of the blood-retinal barriers and cystoid macular edema. Surv Ophthalmol 1984; 28:485-92. 16. Miyake K, Sugiyama S, Norimatsu I, Ozawa T. Aqueous prostaglandins in perSistent cystoid macular edema secondary to vitreous incarceration: effects of pars plana vitrectomy. Jpn J Ophthalmol 1980; 24:335-45. 17. Stjernschantz J. Autacoids and neuropeptides. In: Sears ML, ed. Pharmacology of the Eye. Berlin: Springer-Verlag, 1984; 311-65. 18. Stjernschantz J, Sherk T, Borgeat P, Sears M. Intraocular effects of lipoxygenase pathway products in arachidonic acid metabolism. Acta Ophthalmol 1984; 62: 104-11. 19. Fung WE. Results of the vitrectorny/aphakic cystoid macular edema study. Abstract. Ophthalmology 1984; 91 (9S):67. 20. Katzen LE, Fleischman JA, Trokel S. YAG laser treatment of cystoid macular edema. Am J Ophthalmol 1983; 95:589-92. 21. Steinert RF, Puliafito CA. The Nd-YAG Laser in Ophthalmology; Principles and Clinical Applications of Photodisruption. Philadelphia: WB Saunders, 1985; 115-23. 22. Kraff MC, Sanders DR, Jarnpol LM, Lieberman HL. Effect of an ultraviolet-filtering intraocular lens on cystoid macular edema. Ophthalmology 1985; 92:366-9. 23. Jampol L. Aphakic cystoid macular edema; an hypothesis. Arch Ophthalmol, In Press.
Ab$tract: Major advances in the pharmacologic therapy of aphakic cystoid macular edema (ACME) have not occurred since 1982. Topical nonsteroidal anti-inflammatory agents are still not commercially available for ocular therapy. Topical indomethacin remains the one agent which has been proven to be of prophylactic value for angiographic aphakic cystoid macular edema although other non-steroidal agents may also work. The therapeutic value of these compounds for established ACME remains uncertain. No prospective randomized prophylactic or therapeutic trials of either topical or systemic corticosteroids have been performed. [Key words: Aphakic cystoid macular edema, corticosteroids, indomethacin, prophylaxis, prostaglandins.] Ophthalmology 92:807-810, 1985
In 1982, I reviewed the pharmacologic therapy of aphakic cystoid macular edema (ACME). I The following points were made: 1. Prospective masked randomized clinical trials are necessary to evaluate prophylaxis or therapy because of the highly variable clinical course. 2. The incidence of angiographic ACME is much greater than clinically significant macular edema. The small number of patients with clinically significant cystoid macular edema makes studies of this condition difficult. Studies of angiographic ACME mayor may not be relevant to clinically significant cystoid macular edema. 3. Topical and probably systemic indomethacin decrease the incidence of angiographic ACME but a sustained effect beyond one year or an effect on visual acuity has not been demonstrated. From the Northwestem University Medical School, Chicago. Presented at the Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 11-15, 1984. Reprint requests to Lee M. Jampol, MD, 303 E. Chicago Avenue, Chicago, IL 60(311.
4. No pharmacologic agent has been demonstrated to be of proven value for the therapy of established ACME. 5. Theoretical considerations suggest a possible additive effect of corticosteroids and non-steroidal antiinflammatory agents (such as indomethacin). The purpose of this paper is to update the current state of knowledge in regard to pharmacologic prophylaxis and therapy of ACME. .
TOPICAL NONSTEROIDAL ANTIINFLAMMATORY AGENTS To date (March 1985), no topical nonsteroidal antiinflammatory drug for ophthalmology has been approved by the Federal Drug Administration. Clinical trials with investigational protocols have continued with at least three different nonsteroidal anti-inflammatory agents}-IO Topical indomethacin continues to be a favorite medication in studies of aphakic ACME (Tables 1, 2). Both aqueous suspensions and oil-based solutions have been utilized. Topical flurbiprofen has recently been used as an anti-inflammatory agent for corneal and anterior 807
OPHTHALMOLOGY
•
JUNE 1985 •
VOLUME 92
•
NUMBER 6
Table 1. Pharmacologic Prophylaxis of Aphakic CME (Studies since last review') Investigator
Route
Duration and Dosage
Suprofen (0.5%, 1%)
Datiles et al 2
Topical
qid for 70 days
Yes
Indomethacin (1%)
Hollwich et all
Topical
qid for 3 months
Yes
Indomethacin (1%)
Urner-Bloch 6
Topical
qid for 12 weeks
Yes
Indomethacin (1%)
Yamaaki et al 3
Topical
tid for 4 weeks
Uncertain
Agent
Randomized
Result Trend toward reduced CME at 4 and 10 weeks Decreased CME 8-10 weeks postop Decreased CME 6 and 12 weeks postop Trend toward reduced CME 6-9 weeks postop
Comment Numbers too small; results not statistically significant No effect on visual acuity Numbers too small; results not statistically significant
CME = cystoid macular edema; qid = four times daily; tid = three times daily.
segment inflammation in animals and patients. 5 It has also been tested to determine its effect upon the pressure rise following argon laser trabeculoplasty.4 Some antiinflaI11matory effect has been demonstrated. To my knowledge, flurbiprofen has not been utilized in studies of aphakic ACME. An additional topical non-steroidal agent, suprofen, lias recently been tested for the prophylaxis of pseudophakic cystoid macular edema2 (see below).
SYSTEMIC NONSTEROIDAL ANTIINFLAMMATORY AGENTS An ever increasing spectrum of nonsteroidal antiinflammatory agents that inhibit prostaglandin synthesis is being utilized in medicine. The presently available agents have recently been reviewed. I I Systemic toxicity IS a common finding with many of these drugs. The most extreme example of this is benoxaprofen, a highly effective nonsteroidal anti-inflammatory drug that has been removed from the market because of hepatic and renal toxicity. Side effects of other nonsteroidal agents are commonly seen. PreVious trials in ophthalmology have also accentuated side effects of systemic indomethacin.12 Although in selected cases systemic nonsteroidal anti-inflammatory agents may be required, an effective topical formulation is more desirable.
RECENT CLINICAL TRIALS PROPHYLAXIS OF ACME
Several additional clinical trials have confirmed previous observations that topical indomethacin is effective in the prophylaxis of angiographic ACME (Table 1)03,6,7 The number of patients in these trials is small and the study design is less rigorous than previously reported trials. I In some studies, the number of patients is so small that only a trend has been seen that is not statistically significant. 3 There is no reason to question the previous conclusion that the incidence of angiographic ACME is decreased by the prophylactic administration of topical indomethacin. Additional trials in this area are not indicated. It is still true that an effect on visual acuity or even a sustained effect on ACME (beyond 1 year) has never been demonstrated. Datiles and associates have reported a prophylactic trial of a new topical prostaglandin synthesis inhibitor, suprofen.2 This agent facilitates mydriasis during the ca4tract surgical procedure. A trend towards a diminished incidence of angiographic ACME was seen in this study four and ten weeks after surgery (with the application of either 0.5% or 1% suprofen). The number of patients in this study was very small and the results were not statistically significant.
Table 2. Pharmacologic Therapy of Aphakic CystOid Macular Edema (ACME) (Studies since last review') Agent
Investigator
Route
Indomethacin (1%)
Cohen and Yannuzzi8
Topical
Combination of prednisolone acetate (1%) and indomethacin (1%) Indomethacin (1%)
Yannuzzi, Leibo, Sisc08
Miyake9
808
Duration and Dosage
Randomized
Result
Comment
Yes
"Near significant" effect on ACME
Study not yet reported in detail
Topical
1 month, frequency not reported Not described
No
80% of patients experienced visual improvement
50% relapses; Study not reported in detail
Topical
Not described
No
7 cases "responded " to indomethacin
Anecdotal
JAMPOL
•
CYSTOID MACULAR EDEMA
Unfortunately, no recent clinical trials have addressed value of topical, periocular, or systemic corticosteroIds for the prophylaxis of ACME. It has, however, been shown that topical corticosteroids and indomethacin prevent breakdown of the blood-aqueous barrier after cataract surgery, as measured by fluorophotometry.13 th~
OTHER CLINICAL STUDIES ON PROSTAGLANDINS AND ACME
THERAPY OF ESTABLISHED ACME
Miyake has measured prostaglandins in the aqueous humor of aphakic eyes in patients with vitreous incar• 16 ceratlOn. He showed elevated values. These values decreased following vitrectomy. Miyake iO has also shown that the incidence of angiographic CME in patients ut;tdergoing retinal detachment surgery can be diminished WIth the prophylactic use of indomethacin.
S~nce m~ last c~rtlcosterOids or
review, no therapeutic trials involving non-steroidal agents have been reported WIth the exception of brief notes by Yannuzzi8 and Miyake9 (Table 2). Yannuzzi mentions two clinical trials. In a randomized study utilizing topical indomethacin for the therapy of established ACME a "near significant effect" was mentioned. However, the details of this report have not appeared and we do not know if impr~ved vis~al acuity or decreased clinical or angiographIC cystOid macular edema was the end point. Yannuzzi also briefly mentions an uncontrolled trial of a combination of 1% prednisolone and 1% indomethacin for the therapy of established ACME. This was a consecutive series that was not randomized. The authors reported that 80% of the patients showed visual improvement. A high relapse rate was noted and an "on and off" effect of therapy was seen in many patients. Unfortunately, the fact that this study was not controlled makes interpretation of the results difficult. Miyake9 also describes patients with established ACME who have responded to topical indomethacin. Again, an "on and off" phenomenon with frequent relapses was seen. A similar effect was previously reported with topical fenoprofen. 14
ADDITIONAL STUDIES OF TOPICAL NONSTEROIDAL AGENTS Using fluorophotometry, Kraff and Sanders have shown that the combination of topical corticosteroids and indomethacin was more effective in reducing breakdown of the blood-aqueous barrier following cataract surgery than either topical indomethacin or topical corticosteroids alone. 13 In addition, each of these agents alone was more effective than placebo. Although one cannot necessarily extrapolate from fluorophotometric measurements to the presence of cystoid macular edema this study adds logical support to the supposition that ~ cO?lbination of corticosteroids and nonsteroidal agents mIght be more effective for either prophylaxis or therapy of ACME. Yamaaki and associates in a small trial suggested an association between leakage on iris angiography and the presence of ACME. 3 This is not surprising in view of the presence of breakdown of the blood-ocular barriers in both situations. Indomethacin was effective in diminishing the increased iris leakage and there was a trend towards a beneficial effect on angiographic cystoid macular edema in this study. Cunha-Vaz 15 has also suggested an association between breakdown of the blood-ocular barriers and ACME.
OTHER MEDIATORS OF CYSTOID MACULAR EDEMA It is possible that ACME may be partially mediated by other substances besides prostaglandins. 17 Other "~andi?ates" include neuropeptides (eg. substance P), hlstamme, and the kinins. Recent studies suggest that the miosis seen with inflammation or eye trauma may be mediated by substance p.17,18 However, breakdown of t~e blood-ocular barriers (at least the blood-aqueous bam:r) seems r;nore resistant to this peptide. No highly effectlve nontOXIC substance P antagonist exists at present. Arachidonic acid can be converted by lipoxygenases to other eicosanoids, including the leukotrienes. 17 Any role of these substances in cystoid macular edema is h~g~ly speculative. Effective nontoxic lipoxygenase inhIbItors would be helpful to study this possibility.
OTHER APPROACHES TO ACME Surgical therapy for aphakic cystoid macular edema remains a possibility especially in eyes with vitreous incarceration in the wound. Fung has reported a favorable effect of surgical vitrectomy on ACME in a randomized prospective controlled trial. 19 YAG laser vitreolysis may be similarly effective in such eyes although to date only uncontrolled trials have been reported?O,21 Randomized trials of this therapy are necessary. Kraff and associates have reported a possible role of post-operative ultraviolet light exposure in the development of angiographic ACME.22 Filtering UV light with a chromophore in the intraocular lens reduced the angiographic incidence of ACME. No effect on visual acuity was seen. The effect of near ultraviolet radiation on ACME could be mediated by generation of free radicals,23 which are known to facilitate the synthesis of prostaglandins or other mediators. The possible import~nc.e of this pathway in the development of visually sIgmficant ACME remains uncertain, and the long-term safety of the ultraviolet filtering chromophores available presently requires further studies.
ACKNOWLEDGMENT David Shoch, MD assisted with the translation of references 6 and 7.
809
OPHTHALMOLOGY
•
JUNE 1985 •
REFERENCES 1. Jampol LM. Pharmacologic therapy of aphakic cystoid macular edema; a review. Ophthalmology 1982; 89:891-7. 2. Datiles MB, Stark WJ, Fagadau WR, et al. Pseudophakic CME: clinical trial of a new topical prostaglandin synthesis inhibitor. Ophthalmology, In Press. 3. Yamaaki H, Hendrikse F, Deutman AF. Iris angiography after cataract extraction and the effect of indomethacin eyedrops. Ophthalmologica 1984; 188:82-6. 4. Hotchkiss ML, Robin AL, Pollack IP, Quigley HA. Nonsteroidal antiinflammatory agents after argon laser trabeculoplasty; a trial with flurbiprofen and indomethacin. Ophthalmology 1984; 91 :969-74. 5. Hurvitz LM, Spaeth GL, Zakhour I, et al. A comparison of the effect of flurbiprofen, dexamethasone, and placebo on cyclocryotherapyinduced inflammation. Ophthalmic Surg 1984; 15:394-9. 6. Urner-Bloch U. Pravention des zystoiden Makulaodems nach Kataraktextraktion durch lokale Indomethacin Applikation. Klin Monatsbl Augenheilkd 1983; 183:479-84. 7. Hollwich F, Jacobi K, Kuchle H-J, et al. Zur Prophylaxe des zystoiden Makulaodems mit Indometacin-Augentropfen. Klin Monatsbl Augenheilkd 1983; 183:477-8. 8. Yannuzzi LA. A perspective on the treatment of aphakic cystoid macular edema. Surv Ophthalmol 1984; 28:540-53. 9. Miyake K. Indomethacin in the treatment of postoperative cystoid macular edema. Surv Ophthalmol 1984; 28:554-68. 10. Miyake K, Miyake Y, Maekubo K, et al. Incidence of cystoid macular edema after retinal detachment surgery and the use of topical indomethacin. Am J Ophthalmol 1983; 95:451-6. 11. Jampol LM. Nonsteroidal anti-inflammatory drugs. Focal Points: Clinical Modules for Ophthalmologists 1984; Module 3.
P1n
VOLUME 92
•
NUMBER 6
12. Klein RM, Katzin HM, Yannuzzi LA. The effect of indomethacin pretreatment on aphakic cystoid macular edema. Am J Ophthalmol 1979; 87:487-9. 13. Sanders DR, Kraff M. Steroidal and nonsteroidal anti-inflammatory agents; effect on postsurgical inflammation and blood-aqueous humor barrier breakdown. Arch Ophthalmol 1984; 102:1453-6. 14. Burnett J, Tessler H, Isenberg S, Tso MOM. Double-masked trial of fenoprofen sodium: treatment of chronic aphakic cystoid macular edema. Ophthalmic Surg 1983; 14:150-2. 15. Cunha-Vaz JG, Travassos A. Breakdown of the blood-retinal barriers and cystoid macular edema. Surv Ophthalmol 1984; 28:485-92. 16. Miyake K, Sugiyama S, Norimatsu I, Ozawa T. Aqueous prostaglandins in perSistent cystoid macular edema secondary to vitreous incarceration: effects of pars plana vitrectomy. Jpn J Ophthalmol 1980; 24:335-45. 17. Stjernschantz J. Autacoids and neuropeptides. In: Sears ML, ed. Pharmacology of the Eye. Berlin: Springer-Verlag, 1984; 311-65. 18. Stjernschantz J, Sherk T, Borgeat P, Sears M. Intraocular effects of lipoxygenase pathway products in arachidonic acid metabolism. Acta Ophthalmol 1984; 62: 104-11. 19. Fung WE. Results of the vitrectorny/aphakic cystoid macular edema study. Abstract. Ophthalmology 1984; 91 (9S):67. 20. Katzen LE, Fleischman JA, Trokel S. YAG laser treatment of cystoid macular edema. Am J Ophthalmol 1983; 95:589-92. 21. Steinert RF, Puliafito CA. The Nd-YAG Laser in Ophthalmology; Principles and Clinical Applications of Photodisruption. Philadelphia: WB Saunders, 1985; 115-23. 22. Kraff MC, Sanders DR, Jarnpol LM, Lieberman HL. Effect of an ultraviolet-filtering intraocular lens on cystoid macular edema. Ophthalmology 1985; 92:366-9. 23. Jampol L. Aphakic cystoid macular edema; an hypothesis. Arch Ophthalmol, In Press.