Alay S. Banker

Vision-threatening Complications of Surgery for Full-thickness Macular Holes

OBJECTIVE To study complications of vitrectomy surgery for full-thickness macular holes. DESIGN A multicentered, randomized, controlled clinical trial. PARTICIPANTS Community and university-based ophthalmology clinics. INTERVENTION Standardized macular hole surgery versus observation. MAIN OUTCOME MEASURES Assessment of anatomic and visual outcomes and determination of postoperative complications at 12 months after randomization. RESULTS Posterior segment complications were noted in 39 eyes (41%). The incidence of retinal pigment epithelium (RPE) alteration and retinal detachment (RD) were 33% and 11%, respectively. One RD due to a giant retinal tear resulted in a visual acuity of light perception. Other complications included a reopening of the macular hole in 2 eyes (2%), cystoid macular edema in 1 eye (1%), a choroidal neovascular membrane in 1 eye (1%) and endophthalmitis in 1 eye (1%). Eyes with complications had significantly worse visual acuity outcomes as determined by the Early Treatment Diabetic Retinopathy Study, Word Reading, and Potential Acuity Meter charts (P < 0.01 for all comparisons). Eyes with macular holes greater than 475 microns were more than twice as likely to have complications than eyes with holes less than 475 microns (odds ratio [OR] = 2.2, P = 0.07). Before surgery, the stage of the hole was related to postoperative RPE changes (P < 0.0001) and the occurrence of postoperative RD (P = 0.0002). Intraoperative trauma was related to the occurrence of these complications (P < 0.0001 for RPE changes, P = 0.02 for RDs). Epiretinal membrane removal was related to RPE changes (P = 0.02) but not RDs. CONCLUSIONS The RPE alterations and RDs are common after macular hole surgery and result in significantly reduced postoperative visual acuity. The RPE changes may be related to surgical trauma or light toxicity. Further efforts to reduce complications associated with macular hole surgery are indicated.

The effect of deep posterior subtenon injection of corticosteroids on intraocular pressure

PURPOSE To investigate the effect of posterior subtenon injections of corticosteroids on intraocular pressure in a variety of ocular diseases. METHODS We retrospectively analyzed 202 consecutive posterior subtenon corticosteroid injections (148 of methylprednisolone acetate, 80 mg, and 54 of triamcinolone acetonide, 40 mg) in 63 eyes of 55 patients (26 male, 29 female; mean age +/- SD, 60.17 +/- 26.55 years). All patients had received topical or systemic corticosteroids before the injection, and no rise in intraocular pressure had been noted. Preinjection and postinjection intraocular pressure measurements were compared by two-tailed paired t test. Statistical analysis was performed separately by patient (first injection of first injected eye), by eye (first injection of each eye), and by all injections. To detect increase in intraocular pressure during follow-up, statistical analysis was performed separately 14 to 90 days, 91 to 150 days, and 151 to 270 days after injection. RESULTS No statistically significant difference was found between preinjection and postinjection intraocular pressure measurements. A power calculation in the most stringent subanalysis (by patient) proved that there is only a 3.87% chance to statistically miss a clinically significant rise in intraocular pressure from 15 to 21 mm Hg. CONCLUSIONS Posterior subtenon injection of corticosteroids does not cause an increase in intraocular pressure. All patients in our study had been treated previously with topical or systemic corticosteroids and did not react with an excessive increase in intraocular pressure. This safety of repository corticosteroids may therefore not apply to patients whose status in responding to corticosteroids is not known.

Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization

PURPOSE To assess the role of bevacizumab in inflammatory ocular neovascularization. DESIGN Retrospective, multicenter, consecutive case series of inflammatory ocular neovascularization. METHODS Patients with inflammatory ocular neovascularization of varying causes for whom standard therapy failed were treated with intravitreal injection of bevacizumab. Main outcome measures included improvement of best-corrected visual acuity (BCVA) expressed in logarithm of minimum angle of resolution units, response of inflammatory ocular neovascularization by funduscopy and angiography, and decrease in central foveal thickness as measured by optical coherence tomography at the three-month follow-up. RESULTS At the three-month follow-up, 84 eyes of 79 patients had been treated with a mean of 1.3 injections (range, one to three). Thirty-four eyes showed juxtafoveal choroidal neovascularization (CNV), 34 eyes showed subfoveal CNV, eight eyes showed peripapillary CNV, and 11 eyes showed neovascularization of the disc (NVD) or neovascularization elsewhere (NVE). BCVA improved 2.4 lines from 0.68 (6/28 or 20/94) to 0.44 (6/17 or 20/55) (P < .001). BCVA improved by one to three lines in 34.5% of the eyes, by four to six lines in 16.7% of the eyes, and by more than six lines in 14.2% of the eyes. Function was unchanged in 23.8% of the eyes. BCVA worsened in 10.7% (zero to three lines in 7.1%, more than four lines in 3.6%). Central foveal thickness decreased from baseline 346 to 252 microm (P < .001). For CNV, 32 eyes (43.2%) had complete regression after the injection, 27 (36.5%) had partial regression, five (6.8%) had no response, and 10 eyes (13.5%) were not evaluated by the contributors. For NVD or NVE, seven eyes (63.6%) had complete regression of new vessels and four eyes (36.4%) had partial regression after the injection. CONCLUSIONS Intravitreal bevacizumab led to short-term significant visual improvement and regression of inflammatory ocular neovascularization in a wide variety of inflammatory ocular diseases.

Intraocular Pressure and Aqueous Humor Dynamics in Patients With AIDS Treated With Intravitreal Cidofovir (HPMPC) for Cytomegalovirus Retinitis

PURPOSE To evaluate the decrease in intraocular pressure associated with cidofovir (1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate; HPMPC) intravitreal injections. METHODS We followed up 97 eyes of 63 patients with acquired immunodeficiency syndrome (AIDS) who had cytomegalovirus retinitis and had been treated with up to nine 20-microgram intravitreal cidofovir injections. Measurements were taken at baseline, between 2 and 3 weeks, and at 5 to 6 weeks after injections. Anterior chamber fluorophotometry was studied in seven eyes (four patients) before and after injections. Ciliary body anatomy was evaluated in two patients. RESULTS After the first intravitreal injection, mean intraocular pressure was 2.2 mm Hg lower than that at baseline at 2 to 3 weeks (P < .001) and 1.3 mm Hg lower than at baseline at 5 to 6 weeks (P = .0025). After the second injection, mean pressure was 2.6 mm Hg lower at 2 to 3 weeks (P = .0013) and 1.5 mm Hg lower at 5 to 6 weeks (P = .043). After subsequent injections, however, the decrease was less than 1 mm Hg, suggesting that a plateau had been reached. Pressure in eyes with anterior uveitis after the first injection was lower than that in eyes without anterior uveitis (P < .0001). The mean rate of aqueous flow decreased from 2.8 to 1.9 microliters per minute 2 to 4 weeks after injection (P < .015). Ultrasound biomicroscopy disclosed that severe hypotony after cidofovir injections is associated with ciliary body atrophy. CONCLUSIONS Intraocular pressure decreases after the initial 20-microgram cidofovir intravitreal injection. However, eyes stabilize (pressure plateaus) after three injections. Effects on the ciliary body are the main cause of the decrease after cidofovir injections.

Adverse events and autopsy findings after intravitreous cidofovir (HPMPC) therapy in patients with acquired immune deficiency syndrome (AIDS)

OBJECTIVE The purpose of the study is to evaluate the adverse events and autopsy findings in a series of consecutive 20-microg intravitreous cidofovir injections at a single institution. DESIGN The study design was a nonrandomized, consecutive case series. PARTICIPANTS Seventy-six patients with acquired immune deficiency syndrome with cytomegalovirus retinitis were studied prospectively. Sixty-three patients had 1 months follow-up or longer, and this comprised the study group. In addition, histopathologic findings from 18 eyes of 9 patients were studied at autopsy. INTERVENTION A total of 296 injections of 20 microg cidofovir were given in 115 eyes. Sixty-three patients who had 246 injections in 93 eyes had 1 months follow-up or longer for the evaluation of adverse events. MAIN OUTCOME MEASURES Postinjection chronic hypotony associated with permanent visual loss, transient hypotony, iritis, and its long-term sequela (posterior synechia and cataract, retinal detachment, extraocular cytomegalovirus involvement) were the outcomes of interest in this study. Additionally, light and electron microscopic studies of human eyes were performed. RESULTS The most severe adverse event was postinjection chronic hypotony. This phenomenon was associated with permanent visual loss. This was observed in 1% of the injections and 3% of the eyes of the patients (95% confidence interval, 0%-6%). Transient hypotony associated with mild-to-moderate visual loss developed in 14%, but vision recovered to baseline levels in these eyes subsequently. Analysis showed that transient hypotony in the injected eye could predict postinjection chronic hypotony in the fellow eye (two-tailed Fishers exact test, P = 0.02). The incidence of iritis was 32%; posterior synechia and cataract were the long-term sequela of the iritis and developed in 19% and 11% of the eyes, respectively. The incidence of retinal detachment was lower (6%). Histopathologic evaluation of the eyes showed mild-to-moderate atrophy of the nonpigmented epithelium of the ciliary body and no other evidence of intraocular toxicity. CONCLUSIONS The most serious adverse event was postinjection chronic hypotony, which occurred in 3% of eyes. Episodes of transient hypotony appear to indicate that the fellow eye was predisposed to chronic hypotony. Therefore, it may be prudent to give intravitreous injections at least 2 weeks apart in the fellow eye to evaluate the clinical response of the injected eye.

Long-term Visual Outcomes of Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization

PURPOSE To assess the long-term role of bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in inflammatory ocular neovascularization. DESIGN Retrospective multicenter consecutive case series of inflammatory ocular neovascularization. METHODS settings: Multicenter institutional and private practices. STUDY POPULATION Patients with inflammatory ocular neovascularization in one or both eyes of varying etiologies who failed standard therapy. intervention: Intravitreal injection of bevacizumab. MAIN OUTCOME MEASURES Improvement of best-corrected visual acuity (BCVA) expressed as logarithm of minimal angle of resolution (logMAR), and decrease in central foveal thickness as measured by optical coherence tomography at 6, 12, 18, and 24 months of follow-up. RESULTS Mean logMAR BCVA (central foveal thickness) following intravitreal bevacizumab was as follows: baseline, 0.65 (6/27 or 20/90) (338 microm; 99 eyes of 96 patients); 6 months, 0.42 (6/16 or 20/53) (239 microm; 2.0 injections; 81 eyes); 12 months, 0.39 (6/15 or 20/49) (241 microm; 2.3 injections; 95 eyes); 18 months, 0.40 (6/15 or 20/50) (261 microm; 3.0 injections; 46 eyes); and 24 months, 0.34 (6/13 or 20/44) (265 microm; 3.6 injections; 27 eyes). Paired comparisons revealed significant visual improvement at 6 months of 2.4 lines (P = .000), at 12 months of 2.5 lines (P = .000), at 18 months of 2.5 lines (P = .001), and at 24 months of 2.2 lines (P = .013). Paired comparisons revealed significant central foveal flattening at 6 months of 78 microm (P = .000), at 12 months of 85 microm (P = .000), at 18 months of 90 microm (P = .003), and at 24 months of 77 microm (P = .022). Three eyes developed submacular fibrosis and 1 eye submacular hemorrhage. CONCLUSION Intravitreal bevacizumab led in the long-term to significant mean visual improvement of > or =2.2 lines and significant foveal flattening in a wide variety of inflammatory ocular diseases without major complications.

Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.

Purpose: To assess the outcomes of the intravitreal administration of methotrexate in uveitis. Methods: Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy. Results: Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan–Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection. Conclusion: In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

Triamcinolone Acetonide Concentration of Aqueous Humor after Decanted 20-mg Intravitreal Injection

PURPOSE To characterize the concentration-time profile of triamcinolone acetonide (TA) in human aqueous after a single, 20-mg, intravitreal injection. DESIGN Case series. PARTICIPANTS Seven patients and 10 eyes that received intravitreal injection of the decanted 20 mg of TA. METHODS Fifty microliters of aqueous were sampled from each intravitreally TA-injected eye at postinjection monthly interval and the samples were subjected to liquid chromatography coupled with tandem mass spectrometric detection for TA. MAIN OUTCOME MEASURES The TA concentration in the aqueous. RESULTS The TA was cleared from the aqueous in a monoexponential manner with a half-life of 29.6 days and clearance coefficient of 0.0234 (1/day). The extrapolated maximum TA concentration in aqueous was about 3312 ng/ml and the area under the curve was 74,017 day x ng/ml. CONCLUSIONS The TA concentration in human aqueous could stay above therapeutic concentration for 150 days (5 half-lives with remaining TA concentration of 104 ng/ml) after a 20-mg intravitreal injection, suggesting an even longer therapeutic concentration of TA in vitreous.

Evaluation of a novel lipid prodrug for intraocular drug delivery: effect of acyclovir diphosphate dimyristoylglycerol in a rabbit model with herpes simplex virus-1 retinitis.

BACKGROUND Acyclovir diphosphate dimyristoylglycerol is a lipid prodrug of acyclovir that forms liposomes and provides substantial activity against herpes simplex virus, acyclovir-resistant strains of herpes simplex virus, and human cytomegalovirus. We therefore tested this promising new drug in a rabbit model of herpes simplex retinitis. METHODS A total of 22 pigmented rabbits were pretreated with either acyclovir diphosphate dimyristoylglycerol, ganciclovir, acyclovir, or buffer. Retinae then were inoculated with herpes simplex virus-1 or buffer 1 week after the injection of drug. In another experiment we compared the effects of acyclovir diphosphate dimyristoylglycerol and acyclovir diphosphate dioleoylglycerol on the optical clarity of vitreous. RESULTS Animals injected intravitreally with acyclovir diphosphate dimyristoylglycerol showed retinitis that was less severe than that in animals injected with ganciclovir, acyclovir, and buffer; differences in grading scores of the retinitis between animals injected with acyclovir diphosphate dimyristoylglycerol and those injected with buffer were statistically significant (P = 0.0015). Vitreous and optical media became clear 4 days after acyclovir diphosphate dioleoylglycerol injection compared with 10 days after with acyclovir diphosphate dimyristoylglycerol injections. CONCLUSION Acyclovir diphosphate dimyristoylglycerol had prolonged antiviral activity against herpes simplex virus-1 retinitis in a rabbit model. This drug delivery system, modified to improve optical clarity, may allow long-acting intravitreal treatment of cytomegalovirus retinitis and other retinal diseases.

CHOROIDAL VASCULARITY INDEX IN CENTRAL SEROUS CHORIORETINOPATHY.

Purpose: To evaluate choroidal vascularity index (CVI) in eyes with central serous chorioretinopathy (CSC) using an image binarization tool on enhanced depth imaging using spectral domain optical coherence tomography scans. Methods: In this retrospective cohort study, enhanced depth imaging optical coherence tomography scans of both eyes of patients with CSC were taken at baseline; they were segmented and compared with enhanced depth imaging optical coherence tomography scans of fellow eyes without CSC as well as age-matched healthy subjects. Subfoveal choroidal area (1,500 &mgr;m) was segmented into luminal area and stromal area using image binarization. Choroidal vascularity index was defined as the proportion of luminal area to the total circumscribed subfoveal choroidal area. Results: Eyes with acute CSC (32 eyes) had significantly higher CVI compared with their fellow eyes (27 eyes) (P < 0.0001), 19 eyes with resolved CSC (P < 0.0001) and with 30 eyes of age-matched healthy eyes (P < 0.0001). Fellow eyes of subjects with acute CSC also had significantly higher CVI compared with eyes with resolved CSC (P < 0.0001) and age-matched healthy eyes (P < 0.0001). Conclusion: Increased CVI suggests increased vascular component compared with the stromal component in acute CSC. Increased CVI was noted in fellow eye of the subjects with acute CSC in comparison with age-matched healthy subjects. The CVI could be a useful index for early diagnosis of CSC and to assess the treatment response after laser photocoagulation or photodynamic therapy.