VITRECTOMY FOR VITREOUS HEMORRHAGE ASSOCIATED WITH RETINAL VEIN OCCLUSION: Visual Outcomes, Prognostic Factors, and Sequelae.

PURPOSE: To report the outcomes of pars plana vitrectomy for vitreous hemorrhage (VH) associated with retinal vein occlusion and to identify prognostic indicators. METHODS: Interventional, retrospective consecutive case series between 2015 and 2021. RESULTS: The study included 138 eyes of 138 patients (64 female and 74 male); 81 patients had branch retinal vein occlusion and 57 had central retinal vein occlusion. The mean age was 69.8 years. The mean duration between the diagnosis of VH and surgery was 79.6 ± 115.3 (range, 1-572) days. The mean follow-up was 27.2 months. The logarithm of the minimum angle of resolution visual acuity significantly improved from 1.95 ± 0.72 (Snellen equivalent, 20/1782) to 0.99 ± 0.87 (20/195) at 6 months and to 1.06 ± 0.96 (20/230) at the final visit (both P < 0.001). The visual acuity at 6 months improved by three or more lines in 103 eyes (75%). Postoperative complications during follow-up included recurrent VH in 16 eyes (12%) (of which 8 eyes underwent reoperations), rhegmatogenous retinal detachment in six eyes (4%), and new neovascular glaucoma in three eyes (2%). Worse final visual acuity was significantly associated with older age ( P = 0.007), concurrent neovascular glaucoma ( P < 0.001), central retinal vein occlusion ( P < 0.001), worse preoperative visual acuity ( P < 0.001), postoperative new neovascular glaucoma ( P = 0.021), and postoperative retinal detachment ( P < 0.001). The duration of VH was not associated with visual outcomes ( P = 0.684). Preoperative antivascular endothelial growth factor injections and tamponade did not prevent postoperative recurrent VH. CONCLUSION: Pars plana vitrectomy is effective for VH associated with retinal vein occlusion, regardless of the duration of hemorrhage. However, pre-existing risk factors and postoperative sequelae may limit visual recovery.

Phase 1 Dose-Escalation Study of Plasma Kallikrein Inhibitor THR-149 for the Treatment of Diabetic Macular Edema.

Purpose: The purpose of this study was to evaluate the safety and preliminary efficacy of a single intravitreal injection of 3 dose levels of THR-149 in adults with center-involved diabetic macular edema (DME). Methods: A phase 1, open-label, multicenter 3 + 3 dose-esclation study with 3-month follow-up. The primary endpoint was the incidence of dose-limiting toxicities (DLTs) up to and including the Day 14 visit. Additional key endpoints included the incidence of (serious) adverse events ([S]AEs), mean change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), and additional imaging parameters on widefield fluorescein angiography and optical coherence tomography (OCT) angiography. Results: Twelve subjects were treated: 3 subjects received THR-149 0.005 mg, 3 received 0.022 mg and 6 received 0.13 mg. Baseline ocular characteristics were balanced between subjects at each dose level. There were no DLTs or ocular SAEs, and all subjects completed the study. Six subjects experienced a total of 10 AEs in the study eye; 1 case of mild anterior chamber inflammation was deemed related to THR-149 and/or the injection procedure. Mean change from Baseline in BCVA was +7.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters on Day 14, and +6.4 ETDRS letters by Month 3. CST was variable, and mean CST change from baseline was +30.0 µm at Month 3. There were no clinically meaningful changes in imaging parameters. Conclusions: THR-149 was safe and well tolerated; preliminary efficacy in terms of BCVA improvement was observed. Translational Relevance: This work bridges the gap between basic research and clinical care by providing first in human safety and preliminary efficacy data, supporting the further investigation of THR-149 as a potential treatment for DME.

Resolution of Pseudophakic Cystoid Macular Edema: 2 mg Intravitreal Triamcinolone Acetonide versus 40 mg Posterior Sub-Tenon Triamcinolone Acetonide.

PURPOSE: To compare 2 mg intravitreal triamcinolone (IVT) versus 40 mg posterior sub-Tenon triamcinolone acetonide (STT) for the treatment of eyes with pseudophakic cystoid macular edema. METHODS: A retrospective, single-center review of eyes receiving 2 mg IVT between 3/1/2012-3/1/2017 and 40 mg STT between 1/1/2015-3/1/2017. Visual acuity (VA) and central macular thickness (CMT) were recorded at baseline, 1-, 3-, and 6-month follow-up visits. RESULTS: Forty-five eyes were included in the IVT group and 50 eyes in the STT group. Change in VA from baseline to 1, 3, and 6 months was not significantly different between IVT and STT (6 months: 2.3 lines vs. 2.4 lines, p = .10). The IVT group achieved significantly better CMT improvement from baseline compared to STT at 1 month (255 µm vs. 187 µm; p = .03), but this difference was not present at month 3 (214 µm vs. 212 µm; p = .79) or month 6 (176 µm vs. 207 µm; p = .29). During the 6-month follow-up period, approximately 7% of eyes in the IVT group and 12% of eyes in the STT group developed ocular hypertension (p = .43), and all cases were successfully managed with topical anti-ocular hypertensive therapy or observation. CONCLUSIONS: 2 mg IVT and 40 mg STT both achieved significant improvement in vision and CMT with no significant difference between interventions at 3- and 6-month follow-up.

Endophthalmitis following Intravitreal Anti-Vascular Endothelial Growth Factor Therapy: Changes in Incidence and Outcomes over a 9-Year Period.

Aims: To evaluate whether the incidence, microbial spectrum, and visual outcomes of endophthalmitis following intravitreal injections have changed over time.Methods: Retrospective cohort study of endophthalmitis in eyes receiving intravitreal injection of anti-vascular endothelial growth factor between 2009-2012 and 2016-2017 at a single, large retina practice.Results: A total of 283,315 injections resulted in 96 suspected infectious endophthalmitis cases. Comparing 2009-2012 and 2016-2017, the rate of suspected endophthalmitis changed from 1 in 2,663 injections to 1 in 3,195 injections (p = .37). Visual outcomes 6 months after endophthalmitis were significantly better during the latter period (p = .04), with an average loss of 6.3 lines of VA in 2009-2012 compared to a loss of 3.6 lines in 2016-2017. In multivariate analysis, a "no-talking" policy during injections resulted in a trend towards a decrease in endophthalmitis incidence (p = .08). Cessation of post-injection topical antibiotic use did not independently decrease endophthalmitis incidence (p = .24) when the effect of a "no-talking" policy was taken into account. A lower rate of endophthalmitis was seen after prefilled vs. conventionally prepared ranibizumab syringe use for injection (0.014% vs. 0.035%, respectively), though this difference did not meet statistical significance (p = .16).Conclusion: The incidence of endophthalmitis after intravitreal injection decreased and visual outcomes improved between the periods of 2009-2012 and 2016-2017. A "no-talking" policy during injections was associated with a trend toward a decrease in endophthalmitis rate.

Outcomes of Eyes Lost to Follow-up with Proliferative Diabetic Retinopathy That Received Panretinal Photocoagulation versus Intravitreal Anti-Vascular Endothelial Growth Factor.

PURPOSE: To compare anatomic and functional outcomes in eyes with proliferative diabetic retinopathy (PDR) that were lost to follow-up (LTFU) for more than 6 months after treatment with either intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents or panretinal photocoagulation (PRP). DESIGN: Retrospective cohort study. PARTICIPANTS: Fifty-nine patients who were LTFU immediately after treatment for more than 6 months between September 2013 and September 2016. METHODS: Patients with eyes receiving either intravitreal anti-VEGF treatment or PRP with the next follow-up visit occurring more than 6 months after treatment were identified. Visual acuity (VA) and anatomic outcomes at the visit before being LTFU, the return visit, the 6-month visit after return, the 12-month visit after return, and the final visit were gathered and compared between the 2 treatment groups. MAIN OUTCOMES MEASURES: Visual acuity and anatomic outcomes. RESULTS: Seventy-six eyes of 59 patients were included in the study, of which 30 received IVI with anti-VEGF and 46 received PRP. In the anti-VEGF group, mean VA worsened significantly when comparing the visit before being LTFU (0.43±0.38 logarithm of the minimum angle of resolution [logMAR]) with the return visit (0.97±0.80 logMAR; P = 0.001) as well as with the final visit (0.92±0.94 logMAR; P = 0.01). In the PRP group, mean VA worsened significantly when comparing the visit before being LTFU (0.42±0.34 logMAR) with the return visit (0.62±0.64 logMAR; P = 0.03). However, no significant difference was observed at the final visit (0.46±0.47 logMAR; P = 0.38). There was a significantly greater number of eyes with tractional retinal detachment in the IVI group compared with the PRP group at the final visit (10 vs. 1, respectively; P = 0.005). There was a significantly greater incidence of neovascularization of the iris in the IVI arm compared with the PRP arm at the final visit (4 vs. 0, respectively; P = 0.02). CONCLUSIONS: Eyes with PDR that received only intravitreal anti-VEGF demonstrated worse anatomic and functional outcomes after being LTFU compared with eyes that received PRP. Given the potential sequelae of being LTFU, the choice of treatment for PDR must be considered carefully.

Topical Dorzolamide-Timolol With Intravitreous Anti-Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration.

IMPORTANCE: There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti-vascular endothelial growth factor (VEGF) injections. OBJECTIVE: To evaluate the effect of topical dorzolamide hydrochloride-timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy. DESIGN, SETTING, AND PARTICIPANTS: An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit. INTERVENTIONS: Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study. MAIN OUTCOMES AND MEASURES: Change in central subfield thickness was the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures. RESULTS: Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 µm at enrollment to 334.1 µm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 µm at enrollment to 49.5 µm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 µm at enrollment to 239.9 µm at the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60). CONCLUSIONS AND RELEVANCE: These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.

Combined 23-Gauge PPV and Scleral Buckle Versus 23-Gauge PPV Alone for Primary Repair of Pseudophakic Rhegmatogenous Retinal Detachment.

BACKGROUND AND OBJECTIVE: This review compares 23-gauge pars plana vitrectomy (PPV) alone versus combined 23-gauge pars plana vitrectomy and scleral buckle (PPV/SB) for primary repair of pseudophakic rhegmatogenous retinal detachment (RRD). PATIENTS AND METHODS: A retrospective review of 70 eyes that underwent 23-gauge PPV and 43 eyes that received 23-gauge PPV/SB for pseudophakic RRD. Minimum follow-up was 3 months. Outcome measures included anatomical success, visual acuity, and complication rates. RESULTS: The 23-gauge PPV group achieved primary anatomical success in 58 of 70 cases (83%). Primary success in the PPV/SB group occurred in 36 of 43 cases (84%). Final anatomical success was achieved in all 113 cases (100%). The difference in primary success rates was not statistically significant (P = 1.000, Fisher exact test). Average visual acuity for macula-on RRDs in the PPV group showed a +0.07 logMAR improvement (P = .580) versus a +1.34 improvement (P < .001) in macula-off PPV cases. SB/PPV macula-on cases showed a decrease in logMAR visual acuity by -0.06 (P = .380) while macula-off SB/PPV cases improved by +1.28 (P = .002). There were no significant complications in either group. CONCLUSION: Both 23-gauge PPV and PPV/SB are effective procedures for repairing pseudophakic RRD and exhibit similar rates of success.

INCIDENCE OF SUSTAINED OCULAR HYPERTENSION USING PREPACKAGED VERSUS FRESHLY PREPARED INTRAVITREAL BEVACIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare the incidence of sustained ocular hypertension (OHT) after intravitreal injections of prepackaged versus freshly prepared bevacizumab monotherapy for the treatment of neovascular age-related macular degeneration. METHODS: Charts of 1,216 patients with neovascular age-related macular degeneration receiving intravitreal bevacizumab monotherapy at 2 retina practices using different preparations of bevacizumab between January 1, 2009, and December 31, 2011, were reviewed. Primary outcome was incidence of sustained OHT, defined as intraocular pressure > 25 mmHg with an increase ≥ 6 from baseline on ≥ 2 consecutive visits or requiring treatment. RESULTS: A total of 6,479 injections in 740 eyes of 634 patients were included and 14 eyes (0.81% incidence per eye-year) developed sustained OHT. For eyes receiving prepackaged bevacizumab, 10 of 339 eyes (1.39% incidence per eye-year) developed sustained OHT compared with 4 of 401 eyes (0.39% incidence per eye-year) receiving freshly prepared bevacizumab, giving an incidence rate ratio of 3.55 (95% confidence interval, 0.93-13.49; P = 0.063). All eyes that developed sustained OHT achieved intraocular pressure control with observation or topical therapy alone. CONCLUSION: Incidence of sustained OHT after intravitreal bevacizumab is low. We found a trend toward higher rates of sustained OHT with prepackaged bevacizumab although this difference was not statistically or clinically significant.

Oral eplerenone for treatment of chronic central serous chorioretinopathy: a case series.

BACKGROUND AND OBJECTIVE: To evaluate the effect of oral eplerenone on subretinal fluid, visual acuity, and choroidal thickness in patients with chronic central serous chorioretinopathy (CSCR). PATIENTS AND METHODS: Retrospective review of all patients (14 eyes of 14 patients) monitored for a minimum of 3 months with chronic CSCR who were treated with oral eplerenone in a single multi-physician retina practice. Visual acuity, dilated funduscopic examination, and spectral-domain ocular coherence tomography (OCT) with enhanced depth imaging (EDI) were obtained at each visit. Measurement of subfoveal fluid (SFF) height and choroidal thickness were performed. Two-tailed paired t test was used to calculate statistical significance of pre- and post-treatment variables. RESULTS: At 1 month, 10 of 14 eyes had decreased SFF height on OCT and two eyes had complete resolution of SFF. Mean SFF height decreased from 130 µm to 62 µm (P = .05). Mean choroidal thickness decreased from 315 µm to 282 µm (P = .07). Mean visual acuity improved from logMAR 0.41 to 0.40. At 3 months, 13 of 14 (93%) had decreased SFF on OCT, and nine eyes (64%) had complete resolution of SFF. Mean SFF height decreased to 21 µm (P = .004). Mean choroidal thickness decreased to 253 µm (P = .10). Mean visual acuity improved to logMAR 0.28 (P = .02). CONCLUSION: Oral eplerenone may be effective in treating patients with chronic CSCR.

Bimanual assisted eyelid retraction technique for intravitreal injections.

PURPOSE: To describe an alternative technique for avoiding contact with the lids and eyelashes without the use of a metal lid speculum along with the results in clinical practice. METHODS: Retrospective review of the medical records of all patients undergoing intravitreal injections of bevacizumab and ranibizumab with lid retraction achieved by bimanual assisted eyelid retraction between November 2010 and December 2011. RESULTS: A total of 10,164 consecutive intravitreal injections were performed, of which 3,834 were bevacizumab and 6,330 were ranibizumab. In this cohort of patients, 3 suspected cases of endophthalmitis developed (2 culture-negative), corresponding to a rate of 0.03%. CONCLUSION: The technique of bimanual assisted eyelid retraction for intravitreal injection has a low rate of infection similar to the reported rates using a metal lid speculum.

Serous macular detachment in Waldenström macroglobulinemia: a report of four cases.

PURPOSE: To describe a series of 4 patients with Waldenström macroglobulinemia and serous macular detachment, and propose a mechanism for development of subretinal fluid based on optical coherence tomography (OCT) findings. DESIGN: Retrospective observational case series. METHODS: The records of patients with Waldenström macroglobulinemia and OCT documentation of serous macular detachment at Wills Eye Institute were reviewed. Data collection included clinical examination, as well as findings on fluorescein angiography (FA) and OCT. RESULTS: Four patients (8 eyes) with Waldenström macroglobulinemia and serous retinal detachment were identified. All eyes had varying degrees of venous stasis retinopathy and intraretinal edema overlying the macular detachment. Three patients had no FA leakage, while 1 patient had macular leakage in a petaloid pattern. Focal outer retinal defects within the detached retina were seen in 4 eyes on OCT imaging. In one eye, development of cystoid macular edema was observed before the outer retinal defect and serous macular detachment. All patients with serous macular detachment had some degree of outer retinal disruption. CONCLUSION: Discontinuity of the outer retina within the macular detachment may enable immunoglobulins along with accumulated intraretinal fluid to flow into the subretinal space, creating a serous retinal detachment. Even with systemic treatment of the underlying Waldenström macroglobulinemia, the visual prognosis was guarded.

A novel method of draining intraoperative choroidal detachments during 23-gauge pars plana vitrectomy.

A choroidal detachment may form during pars plana vitrectomy when the infusion line is partially disinserted and fluid is infused into the choroid or suprachoroidal space instead of into the vitreous cavity. We describe a new surgical technique that was used successfully in 4 patients who developed intraoperative choroidal detachments during 23-gauge vitrectomy after the infusion cannula was accidentally partially disinserted. During surgery, the infusion line was disconnected from the partially disinserted cannula and was reconnected to another fully inserted cannula. After resuming infusion into the vitreous cavity, the partially disinserted 23-gauge cannula was left in position and was used to immediately drain the choroidal detachment that had formed intraoperatively. In all 4 patients, the surgery then proceeded without complication.

Ranibizumab for eyes previously treated with pegaptanib or bevacizumab without clinical response.

BACKGROUND AND OBJECTIVE: To assess the safety and efficacy of ranibizumab in patients who had inadequate response to pegaptanib or bevacizumab. PATIENTS AND METHODS: In this single-center study, 19 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) previously treated with pegaptanib (n = 1), bevacizumab (n = 13), or both (n = 5) received 12 monthly ranibizumab injections (0.5 mg). Outcomes were measured from start of previous therapy (baseline) to start of ranibizumab treatment (day 0) through 12 months. RESULTS: No drug- or injection-related adverse events and no serious adverse events were reported. At 6 and 12 months, 4 and 5 patients gained 3 or more lines of VA, respectively; 3 patients lost less than 3 lines of VA at 6 months, and 6 patients lost less than 3 lines at 12 months. At 6 and 12 months, VA increased by a mean (± standard error of the mean) of 2.06 ± 1.23 and 1.17 ± 0.62 lines, respectively. Central retinal thickness decreased by a mean of 62.65 ± 22.46 and 62.16 ± 29.20 µm at months 6 and 12, respectively. When stratified by pigment epithelial detachment (PED) status, patients without PED had better visual and anatomical outcomes than patients with PED. CONCLUSION: Ranibizumab has favorable safety and efficacy profiles for patients with AMD without previous response to pegaptanib or bevacizumab.

Hypotony after 25-gauge vitrectomy using oblique versus direct cannula insertions in fluid-filled eyes.

PURPOSE: To compare intraocular pressure (IOP) and rates of postoperative hypotony with 25-gauge pars plana vitrectomy (PPV) without tamponade using oblique versus direct cannula insertions. METHODS: A prospective consecutive series of eyes that underwent 25-gauge PPV without tamponade using an oblique cannula insertion technique was compared with a historical consecutive series of eyes that underwent 25-gauge PPV without tamponade using direct cannula insertions. IOP was recorded before surgery, on postoperative day 1, and on postoperative week 1. RESULTS: Ninety-five eyes had 25-gauge PPV without tamponade, 55 with oblique cannula insertions and 40 with direct insertions. With oblique insertions, there was no statistically significant difference between mean IOPs measured before surgery, on postoperative day 1, and on postoperative week 1. Only 1 (1.8%) of the 55 eyes had hypotony (IOP,

Short-term outcomes of 25-gauge vitrectomy with silicone oil for repair of complicated retinal detachment.

PURPOSE: To investigate the short-term outcomes of 25-gauge pars plana vitrectomy (PPV) in 18 cases of complicated retinal detachment requiring silicone oil tamponade. METHODS: In this retrospective noncomparative review, the primary outcome measures included postoperative anatomical status, preoperative and postoperative visual acuity and intraocular pressure (IOP), cataract progression, development of keratopathy, and other complications. The average follow-up was 5 months (142 days). RESULTS: Thirteen (72.2%) of 18 patients had attachment postoperatively. There was no difference between preoperative visual acuity and visual acuity at the end of follow-up (P = 0.851). One patient (5.6%) who underwent concomitant penetrating keratoplasty had hypotony (IOP, <6 mmHg) postoperatively and until the end of follow-up. Ocular hypertension in two patients was controlled with antiglaucoma drops. Five (55.6%) of 9 patients who were initially phakic underwent cataract extraction or had documented cataract progression. There were no cases of keratopathy or endophthalmitis. Four patients had intraocular or retinal hemorrhage. Two patients developed significant macular epiretinal membranes, and one developed a parafoveal hole. CONCLUSIONS: Sutureless 25-gauge PPV with silicone oil is a relatively safe and comparable alternative to 20-gauge PPV with silicone oil for repair of complicated retinal detachment.

Intravitreal bevacizumab (avastin) in central retinal vein occlusion.

PURPOSE: To describe the effects of intravitreal bevacizumab in eyes with macular edema resulting from central retinal vein occlusions (CRVO). METHODS: Retrospective consecutive case series of patients diagnosed with macular edema from CRVO who received intravitreal bevacizumab. RESULTS: Thirty eyes of 29 patients with an average age of 72 years (range, 54-87 years) had intravitreal bevacizumab injections. Mean follow-up was 18.1 weeks. Initial mean visual acuity was 20/394. At the 1- and 2-month follow-up, mean visual acuity improved to 20/237 (n = 26, P = 0.04) and 20/187 (n = 21, P = 0.008), respectively. At the 3- and 4-month follow-up, visual acuity improved from 20/228 to 20/157 (n = 15, P = 0.05) and from 20/313 to 20/213 (n = 11, P = 0.03), respectively. No significant changes in visual acuity were found after 4 months though the number of patients in this group was small. Duration of treatment effect following an injection appears to be limited to 2 months for most patients. No ocular or systemic adverse reactions were noted. CONCLUSIONS: The visual benefits of intravitreal bevacizumab for macular edema due to CRVO are apparent early but are not sustained without repeated injections. Larger clinical studies with long-term follow-up will be necessary to better elicit the best regimen for this therapy.