Rosa Y. Kim

Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign).

Purpose While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. Methods Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. Results Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the “flying saucer” sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. Conclusion Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.

Long-term stability of circumferential silicone sponge scleral buckling exoplants

PURPOSE The historical extrusion/explantation rate of silicone sponge scleral buckle exoplants is 3.5 to 24.4%. This contrasts with the published 0.6 to 1.2% explantation rate of solid silicone elements. Previously reported silicone sponge exoplants studies were noncircumferential (quadrantic or multiple). This study was undertaken to assess the long-term stability of 360 degrees circumferentially placed 3 x 5 mm silicone sponge exoplants. METHODS Interventional case series of 840 consecutive circumferentially placed 3 x 5 mm silicone sponge exoplants. A retrospective review of operative reports and patient charts was performed. RESULTS A total of 552 patients had documented follow-up over 1 year. Median follow-up was 32.8 months. Six patients underwent removal of the scleral buckling element (two for diplopia, one acute postoperative infection, and three for extrusion). Median time to removal was 7.3 months. Extenuating circumstances contributed to two of the three extrusions. Of the entire series, fewer than 1% of patients required removal of the silicone sponge implant. Excluding patients with less than 1 year of documented follow-up, the long-term infection/extrusion rate was 0.7%. CONCLUSIONS Circumferentially placed silicone scleral buckling sponge elements are very stable and are well tolerated. The explantation/extrusion rate is comparable to published solid silicone element series.

ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION: Role of Prophylactic Topical Ophthalmic Antibiotics.

Purpose: To determine the rate of postintravitreal injection endophthalmitis and to assess microbiological features and outcomes with and without the use of peri-intravitreal injection topical ophthalmic antibiotics. Methods: Consecutive series of endophthalmitis cases retrospectively identified after intravitreal injection at a multicenter, retina-only referral practice (Retina Consultants of Houston) from January 1, 2011 to December 31, 2014. Prophylactic peri-intravitreal injection topical antibiotics were routinely used during the initial 12-month period (January 1, 2011–December 31, 2011) and not used in the final 24-month period (January 1, 2013–December 31, 2014). Main outcome measures were incidence of endophthalmitis, microbiology results, treatment strategies, and visual outcomes. Results: Of 90,339 intravitreal injections, 30 cases of endophthalmitis were identified (endophthalmitis rate = 0.033%; 95% confidence interval, 0.021–0.045%; or approximately 1 of 3,011 intravitreal injections). The most common organisms isolated were coagulase-negative staphylococci (n = 10, 33%), followed by Streptococcus mitis (n = 2, 7%). Fourteen cases (47%) were culture negative. Peri-intravitreal injection topical antibiotic prophylaxis did not decrease the rate of endophthalmitis (0.035% [95% CI, 0.007–0.064%] with antibiotic use versus 0.021% [95% CI, 0.008–0.033%] without antibiotic use; P = 0.261). Conclusion: The risk of endophthalmitis after intravitreal injection remains low, with coagulase-negative staphylococci and Streptococcus mitis the most common bacterial isolates identified. Prophylactic peri-intravitreal injection topical ophthalmic antibiotic use did not decrease the endophthalmitis rate.

Lucentis using Visudyne study: determining the threshold-dose fluence of verteporfin photodynamic therapy combined with intravitreal ranibizumab for exudative macular degeneration.

Purpose Combination verteporfin photodynamic therapy (vPDT) and antivascular endothelial growth factor (anti-VEGF) therapy may decrease the need for injections while maintaining visual acuity in exudative age-related macular degeneration. This pilot study was designed to determine the threshold fluence dose of vPDT (the dose required to demonstrate an effect on choroidal perfusion) combined with ranibizumab. Methods Seven patients were randomized to sham vPDT (two patients), 20% fluence vPDT (two patients), or 40% fluence vPDT (three patients) in combination with three-monthly intravitreal 0.5 mg ranibizumab injections. Intravitreal ranibizumab was reinjected if disease activity was seen on fluorescein angiography, optical coherence tomography, or clinical examination. Indocyanine green-determined choroidal hypoperfusion was graded in a masked fashion. Results Patients with 20% vPDT had mild hypoperfusion defects at seven days that resolved by week 4 (threshold dose); patients with 40% fluence vPDT had marked hypoperfusion at seven days that persisted as long as 12 months. Recruitment was stopped after limited efficacy was observed. One patient with 20% fluence vPDT lost 19 letters at one year; no other patient lost or gained >10 letters. Central retinal thickness decreased in six of seven patients, but ranibizumab injections did not decrease. Conclusion This pilot study shows that the threshold fluence dose of vPDT (when combined with ranibizumab) is approximately 20% standard fluence, and that mild and transient choroidal hypoperfusion can occur. Forty percent fluence vPDT causes a more prolonged and striking hypoperfusion. Despite hypoperfusion, no decrease in visual acuity or injections required was noted, suggesting that even higher fluence levels of vPDT may be necessary to decrease the number of anti-VEGF injections.

An experimental model of retinal pigment epithelial and neurosensory serous detachment.

Purpose The authors document an animal model of retinal pigment epithelial (RPE) detachments. Methods N-ethylmaleimide (NEM) and sodium iodate (sulfhydryl-alkylating agents) were injected into the vitreous of Dutch pigmented rabbits. Subretinal fluid samples were withdrawn 0.5 and 3 hours after NEM injections and analyzed for albumin content by gel electrophoresis. Selected eyes were examined histologically. Results Injections of 9.2 μg NEM caused wrinkling of the retina within 15 minutes, at which time fluorescein angiography revealed multifocal RPE detachments. At this stage, histologic sections showed moderate choroidal edema and RPE detachment. Elevated retinal detachments developed over the next 15 to 25 minutes. Histologic sections showed massive choroidal edema and RPE fragmentation. The albumin concentration of subretinal fluid rose from 60% of serum level at 30 minutes after NEM to 80% after 3 hours. Sodium iodate did not cause choroidal edema or RPE detachment. Conclusion In rabbits, intravitreal NEM causes the rapid appearance of choroidal edema and RPE detachment, followed by serous retinal detachment. The initial effect probably is caused by an alteration of choroidal vascular permeability. The relationship of these effects to sulfhydryl alkylation is unclear because sodium iodate failed to produce RPE detachments. N-ethylmaleimide effects may model aspects of clinical RPE and serous retinal detachments.

Use of nepafenac (Nevanac®) in combination with intravitreal anti-VEGF agents in the treatment of recalcitrant exudative macular degeneration requiring monthly injections

Purpose The purpose of this study is to determine the efficacy of combining topical nepafenac with monthly intravitreal injections of ranibizumab or bevacizumab in the treatment of recalcitrant exudative macular degeneration. Methods This was a retrospective, consecutive case series of patients with exudative macular degeneration requiring maintenance therapy of antivascular endothelial growth factor ( anti-VEGF) injections at least every 6 weeks, who were started on topical nepafenac. Despite frequent anti-VEGF dosing, all patients included in the study had persistence of any combination of the following: intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Patients underwent pinhole visual acuity, clinical exam, and optical coherence tomography (OCT) at baseline and every follow-up visit. Response to therapy was graded by reviewing quantitative and qualitative OCT data, and statistical analysis was done with paired Student’s t-test. Results Twenty-five patients (average age 77; 14 male and 11 female) were reviewed; the mean number of previous injections was 17.4 (range 3–31). Baseline mean visual acuity was 20/55, and final mean visual acuity after 3 months of treatment was 20/51 (P = 0.13). Monthly mean central foveal thickness measurements were 248, 250, 257, and 247 μm (P = 0.53) at baseline, 1, 2, and 3 months, respectively. By the end of the 3-month time point, qualitative OCT findings on 13 patients treated with nepafenac were classified as stable, 10 as better, and 2 as worse. Conclusions There was no significant change in visual acuity or quantitative OCT measurements, but there appeared to be a mild trend toward improved anatomy and qualitative OCT findings when topical nepafenac was added to monthly anti-VEGF injections in patients with persistent intraretinal cysts, subretinal fluid, and/or pigment epithelial detachment. Further prospective studies with longer follow-up may be warranted.

Selected Clinical Comparisons of Spectral Domain and Time Domain Optical Coherence Tomography

The authors report four cases where spectral domain optical coherence tomography (SD-OCT) imaged pathology not captured by time domain optical coherence tomography (TD-OCT). These cases include one of angioid streaks, two of juxtafoveal telangiectasia, and one of age-related macular degeneration. In each case, the improved images provided by SD-OCT changed either the management of the patient or the counseling of their disease process.