Topical Dorzolamide for the Treatment of Cystoid Macular Edema in Patients With Retinitis Pigmentosa

Grover, Sandeep; Apushkin, Marsha A.; Fishman, Gerald A.

doi:10.1016/j.ajo.2005.12.030

Cited by 143 publications

(104 citation statements)

References 20 publications

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“…Several therapies are used to treat CME in RP patients and include topical or oral administration of carbonic anhydrase inhibitor, [1][2][3][4] periocular or intravitreal injection of steroid, [5][6][7][8][9] intravitreal injection of bevacizumab, 10 photocoagulation, 11,12 or vitrectomy. 13 Although each of these therapeutic measures provides a benefit for some of the patients, there is little information on the pathophysiology, prevalence, or natural course of CME that is associated with RP.…”

Section: Introductionmentioning

confidence: 99%

Photoreceptor integrity and visual acuity in cystoid macular oedema associated with retinitis pigmentosa

Oishi

Otani

Sasahara

et al. 2008

Eye

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Aims To assess the correlation between macular morphology and visual acuity in retinitis pigmentosa (RP) patients with cystoid macular oedema (CME). Design Retrospective cross-sectional study. Patients and methods Forty-one eyes of 25 RP patients with CME. Patients underwent cross-sectional scans with optical coherence tomography (Stratus OCT). Age, total retinal thickness, photoreceptor thickness, and the transverse and vertical lengths of the cystoid space were measured. Correlation between visual acuity and each of the measurements were examined. Additionally, the status of the inner segment/outer segment junction (IS/OS) was classified as being absent, discontinuous, or distinct. Measurements were then compared among the three groups. Results Total retinal thickness or photoreceptor thickness was not correlated with visual acuity. There was a correlation between the transverse length of the cystoid space and visual acuity, although the correlation coefficient was weak (r ¼ 0.30). The logMAR visual acuity in the IS/OS absent group (0.67±0.43) was worse than that seen in the IS/OS discontinuous (0.22 ± 0.19) or IS/OS distinct groups (0.07 ± 0.16) (Po0.001). Conclusions When monitoring CME associated with RP, the status of IS/OS is the essential parameter that needs to be examined.

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Section: Introductionmentioning

confidence: 99%

Photoreceptor integrity and visual acuity in cystoid macular oedema associated with retinitis pigmentosa

Oishi

Otani

Sasahara

et al. 2008

Eye

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“…This may explain why dorzolamide treatment was less effective in rescuing the R219S mutant than the R69H. Given the proven efficacy of CA inhibitors in treating other ophthalmic diseases like glaucoma and cystoid macular edema in RP (25,26), we suggest that CA inhibitors may provide a safe and effective approach to therapy for RP17.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of retinitis pigmentosa associated with apoptosis-inducing mutations in carbonic anhydrase IV

Datta

Waheed

Bonapace

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Missense mutations in the carbonic anhydrase IV (CA IV) gene have been identified in patients with an autosomal dominant form of retinitis pigmentosa (RP17). We used two transient expression systems to investigate the molecular mechanism by which the newly identified CA IV mutations, R69H and R219S, contribute to retinal pathogenesis. Although the R219S mutation drastically reduced the activity of the enzyme, the R69H mutation had a minimal effect, suggesting that loss of CA activity is not the molecular basis for their pathogenesis. Defective processing was apparent for both mutant proteins. Cell surface-labeling techniques showed that the R69H and R219S mutations both impaired the trafficking of CA IV to the cell surface, resulting in their abnormal intracellular retention. Expression of both CA IV mutants induced elevated levels of the endoplasmic reticulum (ER) stress markers, BiP and CHOP, and led to cell death by apoptosis. They also had a dominant-negative effect on the secretory function of the ER. These properties are similar to those of R14W CA IV, the signal sequence variant found in the original patients with RP17. These findings suggest that toxic gain of function involving ER stress-induced apoptosis is the common mechanism for pathogenesis of this autosomal-dominant disease. Apoptosis induced by the CA IV mutants could be prevented, at least partially, by treating the cells with dorzolamide, a CA inhibitor. Thus, the use of a CA inhibitor as a chemical chaperone to reduce ER stress may delay or prevent the onset of blindness in RP17.autosomal dominant ͉ chemical chaperone ͉ ER stress ͉ missense mutation ͉ Naϩ/bicarbonate co-transporter 1

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“…The foveal zone thickness (FZT) was also calculated and recorded as an average of 100 automatic measurements performed in the 1,000-µm ring centered on the foveola by the OCT scanner, using a retinal mapping software available with the device. As suggested by Grover et al [44], both an FT change >16% (mean ± 2 SD) and an FZT change >11% from baseline were considered as statistically significant in the follow-up visits.…”

Section: Methodsmentioning

confidence: 99%

“…The therapeutic approaches previously described are numerous and include the use of periocular or intravitreal steroid injection [21,22,23,24,25], intravitreal bevacizumab [26], grid laser photocoagulation [27,28], pars plana vitrectomy [29] and the administration of topical or oral carbonic anhydrase inhibitors [10,30,31,32,33]. …”

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confidence: 99%

Comparison of Topical Dorzolamide and Ketorolac Treatment for Cystoid Macular Edema in Retinitis Pigmentosa and Usher's Syndrome

et al. 2014

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Purpose: To investigate the topical effect of dorzolamide versus ketorolac on retinitis pigmentosa (RP) and Usher's syndrome (US) macular edema. Methods: Prospective, randomized and interventional study. A total of 28 eyes of 18 patients were included. Five eyes had US, 23 had RP. Fifteen eyes were allocated to ketorolac tromethamine 0.5% (4 drops daily regimen) and 13 eyes to dorzolamide hydrochloride 2% (3 drops daily regimen) treatment groups. Snellen's best-corrected visual acuity (BCVA), foveal thickness (FT) and foveal zone thickness (FZT) measured by Stratus® optical coherence tomography (OCT) were evaluated at baseline, 1, 3, 6 and 12 months after treatment. Results: Patients assigned to ketorolac had a baseline BCVA of 0.37 ± 0.17 logMAR which improved at the end of 1 year to 0.28 ± 0.16 (p = 0.02). Three eyes (20%) of 2 patients improved by 7 letters or more. Mean FT and FZT did not change significantly during the study follow-up. After 1 year of treatment, 4 eyes (27%) of 3 patients showed an improvement of at least 16% of FT and 11% of FZT. Patients assigned to dorzolamide had a baseline BCVA of 0.48 ± 0.34 logMAR which improved in the first 6 months (0.40 ± 0.30; p = 0.01), with a decrease at 1 year (0.42 ± 0.27; p = 0.20). Seven eyes (54%) of 5 patients had an improvement of 7 letters or more. Mean FT and FZT did not change significantly either. After 1 year of treatment, 3 eyes (23%) of 2 patients showed an improvement of at least 16% on FT and 11% on FZT. Conclusions: Results suggest that dorzolamide and ketorolac might improve visual acuity and therefore be of interest in selected cases. No relationship between retinal thickness fluctuation and visual acuity was found. Sample size was a limitation to the study.

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Topical Dorzolamide for the Treatment of Cystoid Macular Edema in Patients With Retinitis Pigmentosa

Cited by 143 publications

References 20 publications

Photoreceptor integrity and visual acuity in cystoid macular oedema associated with retinitis pigmentosa

Photoreceptor integrity and visual acuity in cystoid macular oedema associated with retinitis pigmentosa

Pathogenesis of retinitis pigmentosa associated with apoptosis-inducing mutations in carbonic anhydrase IV

Comparison of Topical Dorzolamide and Ketorolac Treatment for Cystoid Macular Edema in Retinitis Pigmentosa and Usher's Syndrome

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