Effect of less aggressive treatment on diabetic retinopathy severity scale scores: analyses of the RIDE and RISE open-label extension.

OBJECTIVE: To evaluate factors associated with Diabetic Retinopathy Severity Scale (DRSS) changes with less frequent ranibizumab after induction therapy. METHODS AND ANALYSIS: Post hoc analyses of RIDE/RISE and their open-label extension (OLE). Analyses included patients with diabetic retinopathy (DR)/diabetic macular oedema who completed the OLE. Comparisons were made between patients with improved/maintained (≥0 step decrease from OLE baseline (month 36) to month 48) versus worsened (≥1 step increase) DRSS during the OLE. DRSS changes over 12 months were compared between patients randomised to ranibizumab at RIDE/RISE baseline who improved to DRSS score ≤43 at OLE baseline (induced) versus those randomised to sham with DRSS score ≤43 at RIDE/RISE baseline (native). RESULTS: From OLE baseline to month 48, 72% (263/367) of patients improved/maintained DRSS scores. These patients had similar mean best-corrected visual acuity at RIDE/RISE (56.4 letters) and OLE baseline (68.6 letters) versus patients with worsened scores (58.2 and 70.8 letters). Patients who improved/maintained DRSS scores had similar mean central foveal thickness at RIDE/RISE (492 µm) and OLE baseline (196 µm) versus patients with worsened scores (441 and 167 µm). Patients who improved/maintained DRSS scores received a significantly higher (p<0.0001) mean number of pro re nata (PRN) injections (4.4) between OLE baseline and month 48 versus those with worsened scores (2.3). Patients with more severe DR at baseline who achieved mild-to-moderate non-proliferative DR (NPDR) induced by monthly ranibizumab injections were significantly more likely to worsen (p<0.0001) than those with mild-to-moderate NPDR at baseline randomised to sham injections (1.0-step versus 0.1-step worsening). CONCLUSIONS: Most patients improved/maintained DRSS scores with less-than-monthly PRN ranibizumab. Some minimum treatment/monitoring may be necessary to maintain improvements after induction therapy. TRIAL REGISTRATION NUMBERS: NCT00473382/NCT00473330.

PNEUMATIC WITHOUT PEXY: A CASE REPORT OF A RETINAL DETACHMENT REPAIR.

PURPOSE: To present a case of pneumatic retinal detachment repair that did not require retinal pexy. METHODS: Report of a case and review of the literature. RESULTS: Pneumatic retinopexy was performed with a plan for photocoagulation of the retinal tear once the retina was reattached. During postoperative evaluation, the superotemporal retinal tear had operculated and the retina was reattached. No laser or cryopexy was performed, and the retina remained attached during long-term follow-up. DISCUSSION: Addressing traction on the retina and intraocular microcurrents that allow subretinal fluid accumulation is the core principle of detachment repair; if the traction is released, pexy may not be necessary.

Brolucizumab-associated intraocular inflammation in eyes without retinal vasculitis.

PURPOSE: To analyze a series of eyes with brolucizumab-associated intraocular inflammation (IOI) without retinal vasculitis reported to the American Society of Retina Specialists (ASRS). METHODS: The ASRS Research and Safety in Therapeutics (ReST) Committee analyzed clinical characteristics from submitted reports of IOI after brolucizumab. Eyes with retinal vasculitis or that received intraocular antibiotics were excluded. RESULTS: Forty-nine eyes of 45 patients were collected. Mean visual acuity (VA) at baseline was 20/49 (range 20/20 - 5/200). Patients presented with IOI a mean of 24 (range 3-63) days after most recent brolucizumab injection; 61% presented for an unscheduled visit while 39% presented at routine follow-up. Mean VA at IOI presentation was 20/67 (range 20/20 - 3/200). Most common symptoms were floaters (78%) and blurry vision (76%). Pain (20%) and redness (16%) were less common; 3 (6%) eyes were asymptomatic. IOI was anterior only in 18%, posterior only in 31%, and both anterior and posterior in 51% of eyes. Treatment included topical steroids alone in 67% eyes, while 10% eyes received no treatment. Mean VA at last follow-up was 20/56 (range 20/20 - 1/200). Three (6%) eyes lost 3 or more lines and 1 (2%) eye lost 6 or more lines. CONCLUSIONS: Brolucizumab-associated IOI without retinal vasculitis typically presented with a delayed onset of a few weeks. Often, visual acuity decline was relatively mild. Most symptoms resolved and nearly all had a return to baseline VA, but a small percentage of patients had a significant decrease in VA at last follow-up.

Impact of Delayed Time to Treatment on Visual Outcomes in Neovascular AMD: Data From the HARBOR Study.

BACKGROUND AND OBJECTIVE: To determine the potential impact on visual outcomes of delayed treatment initiation in patients with neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: Post hoc analysis of anti-vascular endothelial growth factor treatment-naïve patients with nAMD from HARBOR. Time to treatment was defined as first ranibizumab injection date minus screening date. Comparisons were made between the prompt (≤ 6 days) versus delayed (> 10 days) treatment groups. Main outcome measures were best-corrected visual acuity (BCVA) change over time, BCVA, number of ranibizumab injections, and proportion of 3-line gainers/losers. RESULTS: In HARBOR, more than 50% of patients received their first injection within 7 days of screening, with mean (median) time to treatment of 4.6 (5) and 15.9 (14) days for the prompt and delayed treatment groups, respectively. Mean (95% confidence interval [CI]) BCVA change from baseline to Month 24 was 9.1 (7.4-10.8) and 8.8 (6.7-10.8) Early Treatment Diabetic Retinopathy Study letters in the prompt (n = 395) and delayed (n = 230) treatment groups, respectively. Mean (95% CI) total number of ranibizumab injections for the as-needed arms was 12.4 (11.6-13.3) and 11.4 (10.3-12.4) for the prompt and delayed treatment groups, respectively. CONCLUSION: In HARBOR, time from screening to first ranibizumab injection did not seem to significantly affect mean BCVA change or number of injections. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:62-69.].

PARTICULATE MATTER FROM SYRINGES USED FOR INTRAVITREAL INJECTIONS.

BACKGROUND: Syringes containing anti-vascular endothelial growth factor drugs to treat retinal diseases are prepared in different ways by various parties with syringe selection, preparation, and storage conditions affecting the risk of injecting particles into the vitreous. This study examines particle loads from various syringes over time. METHODS: Four syringes were studied: two plastic transfer syringes lubricated with silicone oil or oleamide, a glass syringe with baked-on silicone, and a lubricant-free polymer syringe. Syringes were rinsed with water or filled with buffer and analyzed over time; particles were quantified by flow imaging. Particle formation in a bevacizumab formulation was also characterized. RESULTS: Insulin syringes consistently showed very high particle counts. Oleamide-lubricated syringes had substantially fewer particles, but showed appreciable increases over time (leading to visible particles). Baked-on silicone glass syringes and lubricant-free polymer syringes both showed low particle levels ≥10 µm. Lubricant-free syringes showed the lowest particle levels ≥1 µm and the lowest particle levels with bevacizumab agitation. CONCLUSION: Syringes have different intrinsic particle loads which can contribute to particle loads in the delivered drug. Oleamide-lubricated transfer syringes, commonly used for bevacizumab repackaging, have time-dependent particle loads and are associated with the formation of visible particles beyond 30 days of storage.

Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab.

PURPOSE: To analyze a case series of retinal vasculitis reported to the American Society of Retina Specialists (ASRS) following Food and Drug Administration approval of brolucizumab for treatment of neovascular age-related macular degeneration. METHODS: The ASRS Research and Safety in Therapeutics Committee analyzed clinical and imaging characteristics from submitted reports of retinal vasculitis after brolucizumab. RESULTS: Retinal vasculitis was reported in 26 eyes of 25 patients (22 [88%] female) after treatment with brolucizumab. Imaging studies were available for 24 of 26 eyes. Most cases (92%) were associated with intraocular inflammation, which presented at a mean of 25 days (range, 3-63 days) after the most recent brolucizumab injection. Mean visual acuity (VA) was 20/52 (range, 20/25-4/200) before the adverse event, 20/151 (range, 20/25-hand motion) at presentation of the adverse event, and 20/243 (range, 20/30-light perception) at last follow-up. Twelve eyes (46%) had a greater than 3-line decrease in VA at final follow-up, and 12 eyes (46%) had a final VA of 20/200 or worse. Analysis of retinal imaging identified vasculopathy that involved retinal arteries (91%), retinal veins (79%), and choroidal vessels (48%). Occlusive disease was apparent on imaging in 83% of eyes. Treatment approaches were varied. CONCLUSIONS: Retinal vasculitis has been identified in a series of eyes following brolucizumab. Although a few eyes in this series were asymptomatic or minimally symptomatic, some eyes had significant vision loss. A careful examination for signs of active inflammation prior to brolucizumab injection is recommended. Once vasculopathy is suspected, angiographic imaging may help define the spectrum of involvement. Optimal treatment strategies remain unknown.

Presumed Solitary Circumscribed Retinal Astrocytic Proliferation in the Fovea With OCT Angiography: A Misnomer.

The retinal lesion known as the presumed solitary circumscribed retinal astrocytic proliferation (pSCRAP) is a benign retinal tumor. Although many of the clinical characteristics of the lesion have been described, much about the pathogenesis of this uncommon tumor is not yet known. Here, the authors report a pSCRAP lesion in the fovea with secondary vision loss occurring in middle age. Structural optical coherence tomography (OCT) scans indicate that the lesion arises from the deep retina or retinal pigment epithelium (RPE), whereas OCT angiography characteristics of the lesion show a lack of intrinsic or paralesional vascular flow, indicating that this lesion is fibrous and likely derived from the RPE or deep retina and not the retinal astrocytes. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:212-214.].

POSTOPERATIVE HEMORRHAGIC OCCLUSIVE RETINAL VASCULITIS: A FORME FRUSTE VARIANT?

PURPOSE: To present a forme fruste variant of hemorrhagic occlusive retinal vasculitis (HORV) after uncomplicated cataract surgery performed with vancomycin in the irrigating solution. METHODS: A report of a single patient who developed HORV; the clinical features and course are described and compared with previously reported cases. RESULTS: Ultra-widefield fluorescein angiography demonstrated an occlusive vasculitis in both eyes 1 week after uncomplicated cataract surgery in which vancomycin was added to the irrigating solution. An extensive systemic evaluation including a hypercoagulable workup, serum electrophoresis, complete blood count, and carotid and cardiac ultrasound was negative. Visual acuity was unaffected, and the patient remained 20/20 in each eye one year after surgery without treatment. This is a markedly different outcome than seen in previously reported cases of HORV. CONCLUSION: Ultra-widefield angiography was helpful to confirming the diagnosis of HORV in this milder case example in a patient who maintained excellent vision. This forme fruste variant of HORV after exposure to vancomycin suggests that the incidence of HORV after cataract surgery may be more common than previously reported. Vigilance, close observation, and broad reporting can help further clarify the incidence and potential adverse effects of routinely using intracameral vancomycin during cataract surgery.

ENDOSCOPY-ASSISTED VITRECTOMY AND MEMBRANE DISSECTION OF ANTERIOR PROLIFERATIVE VITREORETINOPATHY FOR CHRONIC HYPOTONY AFTER PREVIOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To review 6-month outcomes for patients with hypotony secondary to anterior proliferative vitreoretinopathy after previous retinal detachment repair who were treated with endoscopic vitrectomy and anterior membrane dissection. METHODS: Retrospective review. All individuals underwent endoscopic vitrectomy with removal of anterior proliferative vitreoretinopathy involving the ciliary body. Outcome measurements included intraocular pressure (IOP), visual acuity, and development of phthisis bulbi. RESULTS: Fifteen eyes of 15 patients had an average of 4.5 previous intraocular surgeries (range 1-8). Forty Percent of eyes had silicone oil at the time of endoscopic surgery. Six months postoperatively, 4 eyes had IOP >11 mmHg while 11 had IOP <6 mmHg. The nonresponder group was older in age, had more previous intraocular surgeries, and a lower preoperative IOP. There were no differences in visual acuity or the development of prephthisis at any point. No eyes underwent enucleation or evisceration. CONCLUSION: Endoscopy-assisted vitrectomy with removal of anterior proliferative vitreoretinopathy from the ciliary body is an effective treatment for chronic hypotony after previous retinal detachment repair in a minority of cases. The IOP improved in patients who tended to be younger and who had fewer previous intraocular surgeries. Further study is indicated to evaluate long-term outcomes and predictors of surgical success.

Primary intravitreal ranibizumab for high-risk retinopathy of prematurity.

BACKGROUND AND OBJECTIVE: To evaluate initial treatment of high-risk retinopathy of prematurity (ROP) with low-dose intravitreal ranibizumab. PATIENTS AND METHODS: Case series of premature infants with high-risk pre-threshold or threshold posterior ROP receiving primary therapy with 0.2 mg ranibizumab. Pre-treatment and post-injection examination, RetCam (Clarity Medical Systems, Pleasanton, CA) images, fluorescein angiography, resolution of ROP and plus disease, and stability of examinations were assessed. RESULTS: Eight eyes of four infants received primary ranibizumab treatment. Plus disease resolved within 48 hours of unilateral injection, and there was no change in ROP appearance in the contralateral eye. Complete resolution of stage 3 ROP occurred 1 week after injection. Recurrent progressive stage 2 or 3 ROP in mid to anterior zone 2 was noted 8 to 11 weeks after ranibizumab in all eyes. Treatment of recurrent ROP with peripheral laser led to complete ROP regression. Comparison of images before ranibizumab injection to images after ROP recurred demonstrated anterior retinal growth. Retina examinations remained stable without ROP recurrence or detachment at follow-up 8 to 18 months after ranibizumab injection. CONCLUSION: Intravitreal ranibizumab induces rapid, complete regression of high-risk posterior ROP with continued retina growth peripherally. The potential for recurrent ROP after a single 0.2 mg ranibizumab injection for posterior ROP requires vigilant monitoring. Subsequent peripheral laser for ROP recurrences may spare the posterior retina from photocoagulation effects.

How to prevent endophthalmitis after intravitreal injections.

Endophthalmitis is an uncommon but often visually devastating complication of intravitreal injections. This commentary reviews the key aspects and technical components of intravitreal injections and how they may relate to the development of endophthalmitis. Because endophthalmitis is a rare event, data are often lacking on specific aspects of injection technique that may or may not be helpful in preventing infection. What is not in doubt, however, is the utmost importance of using povidone-iodine antisepsis to the ocular surface prior to injection, and maintaining a lash and lid margin-free injection site.

Fuchs endothelial corneal dystrophy: clinical characteristics of surgical and nonsurgical patients.

PURPOSE: To review the patient and clinical characteristics of patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: Review of records for every patient who presented to the Bascom Palmer Eye Institute between 2003 and 2009 whose visit was coded for endothelial corneal dystrophy (International Classification of Diseases, Ninth Revision [ICD9] 371.57), bullous keratopathy (ICD9 371.23), or who underwent a corneal surgery with or without cataract extraction. Demographic, clinical, and ancillary testing data were collected from the time of presentation, diagnosis, and follow-up, and the use, timing, and type of surgical interventions was documented, with 6-month and final visual acuities recorded. RESULTS: A total of 2,370 charts were included in this study, of which 966 patients had a diagnosis of FECD. Of these, 197 patients (21%) received a corneal transplantation procedure. The surgery most often performed was penetrating keratoplasty with or without cataract extraction (66%), followed by endothelial keratoplasty with or without cataract extraction (34%). The risk factors for surgery include worse visual acuity at presentation (20/60 Snellen visual acuity in surgical patients versus 20/40 Snellen visual acuity in nonsurgical patients, P<0.001), greater average central corneal thickness (635 µm versus 592 µm, P<0.001), loss of visual acuity over time (two lines lost versus zero lines lost, P<0.001), increasing age (P<0.001), and male sex (P=0.008). Over half of patients (52%) did not receive surgery despite poor vision. CONCLUSION: During this time period, FECD did not have a consistent pattern for management or treatment, and despite advances in surgical techniques, most patients were still managed without surgery.

Noninfectious inflammation after intravitreal injection of aflibercept: clinical characteristics and visual outcomes.

PURPOSE: To report the presenting features and clinical outcomes of a series of patients with noninfectious inflammation after intravitreal aflibercept injection. DESIGN: Noncomparative consecutive case series. METHODS: Medical records of patients who presented with noninfectious inflammation after intravitreal aflibercept injection between November 18, 2011 and June 30, 2013 were retrospectively reviewed. RESULTS: A total of 20 cases of postinjection inflammation were identified in 5356 aflibercept injections. The patients presented 1-13 days after aflibercept injection (median 3 days); all noted decreased vision, while 3 of 20 (15%) had pain and 2 of 20 (10%) had conjunctival injection. One patient had a hypopyon (0.5 mm), and the average anterior chamber cell was 1.8+ (range 0 to 4+). All eyes had some degree of vitritis (average 1.8+; range 0.5+ to 4+). Patients on average had received 6 prior aflibercept injections (range 0-16). Only 1 patient-the first to present with inflammation in this series-received an intravitreal tap (culture negative) and injection of antibiotics. All patients were managed with frequent topical steroids and were followed closely for signs of improvement. All but 1 patient regained their preinjection visual acuity (average: 33 days; range: 7-73 days). Four patients were subsequently rechallenged with aflibercept, and 1 developed inflammation again after 5 additional aflibercept injections. The overall incidence of inflammation after intravitreal aflibercept injection was 20 of 5356 injections (0.37%) or 19 of 844 patients (2.25%). However, a disproportionate number of cases clustered around 1 provider (17/20, 85%; P < .001 vs all other providers) and around the 2 office locations where this physician primarily worked (16/20, 75%; P < .001 vs 5 other offices). CONCLUSIONS: Noninfectious inflammation after intravitreal aflibercept injection typically presents without pain, conjunctival injection, or hypopyon, and responds to topical steroid therapy. The visual outcomes are generally favorable, though the return to baseline acuity can take many weeks.

Progressive Outer Retinal Necrosis Secondary to Herpes Simplex Virus Type 2.

Progressive outer retinal necrosis is an aggressive form of necrotizing herpetic retinitis that presents in immunocompromised patients. It is usually secondary to varicella zoster virus or, rarely, herpes simplex virus type 1. The authors report a case of progressive outer retinal necrosis associated with herpes simplex virus type 2 in a patient with a history of congenital herpes. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:xxx-xxx.].

Treatment of dystrophic calcification on a silicone intraocular lens with pars plana vitrectomy.

PURPOSE: Dense, vision-obscuring calcification on the posterior aspect of silicone intraocular lenses (IOLs) is often not amenable to neodymium:yttrium-aluminum-garnet capsulotomy, and, in prior reports, has required IOL exchange. We report the successful removal of dense calcium deposition on the posterior surface of a three-piece silicone lens using pars plana vitrectomy (PPV). MATERIALS AND METHODS: A 23-gauge PPV was performed using the Stellaris(®) vitrectomy system. A light pipe was used to retroilluminate the IOL, and a dense fibrous tissue setting with a low cut-rate and high aspiration rate was able to clear the visual axis of the dystrophic calcification without damaging the IOL optic. RESULTS: Visual acuity improved from 20/100 to 20/25. CONCLUSION: Small-gauge PPV may be utilized to remove dense dystrophic calcium deposits on the lens surface in lieu of IOL exchange.

Optical coherence tomography in the preoperative and postoperative management of macular hole and epiretinal membrane.

Optical coherence tomography (OCT) imaging plays an essential role in the diagnosis and treatment of macular diseases, including those of the vitreomacular interface. OCT enables accurate diagnosis and differentiation of full thickness macular hole, lamellar macular hole and epiretinal membrane, with or without the presence of vitreomacular adhesion. This information enables earlier diagnosis and treatment when necessary, and can guide the choice of therapy. OCT is useful to facilitate discussions with patients and manage the visual expectations. Postoperatively, OCT can be helpful to optimise patient comfort and visual outcomes. As the technology continues to improve, OCT will become increasingly critical for all aspects of care for patients with macular hole and epiretinal membrane.

Histopathology of streptococcus mitis/oralis endophthalmitis after intravitreal injection with bevacizumab: a report of 7 patients.

PURPOSE: To report the histopathologic findings of a series of patients from an outbreak of Streptococcal endophthalmitis after intravitreal injection of bevacizumab prepared by a single compounding pharmacy. DESIGN: Case series. PARTICIPANTS: Seven surgical specimens (5 enucleated globes and 2 evisceration specimens) from 7 patients with endophthalmitis after intravitreal injection of bevacizumab. METHODS: Retrospective case series, including clinical data and histopathologic specimens examined by light microscopy. MAIN OUTCOME MEASURES: Review of clinical data included baseline visual acuity, clinical intervention, and time elapsed from injection to loss of globe. Histopathologic specimens were reviewed for pathologic changes at all tissue levels. RESULTS: Seven of 12 total patients (4 women, 3 men; mean age, 77.7 years) from an outbreak of Streptococcus mitis/oralis endophthalmitis after bevacizumab injection ultimately sustained loss of the affected globe, with an average of 139.1 days elapsed between injection and globe loss. Mean time from injection to presentation was 2.86 days (range, 1-6), and all patients were initially treated with vitreous tap and injection. Although histologic review of surgical specimens disclosed a wide range of pathologic tissue changes, recurring patterns of tissue damage were evident. All 5 enucleated globes displayed retinal detachment, fibrous proliferation with cyclitic membrane formation, rubeosis iridis, and secondary angle closure. All 7 specimens displayed persistent choroidal inflammation, in 1 case 208 days after injection. Six of 7 specimens had foci of retinal necrosis. Although vitreous cultures were positive in all cases, no organisms were identified by light microscopy in any of the 7 specimens. CONCLUSIONS: S. mitis/oralis endophthalmitis is a devastating complication of intravitreal injection with bevacizumab with a high rate of globe loss (7 of 12 patients, 58.3%) and a wide variety of severe pathologic tissue changes. Although no organisms were identified in the examined tissues, persistent inflammation was present in all cases, and fibrous proliferation resulted in cyclitic membrane formation and retinal detachment in all enucleated globes. These findings suggest that potential globe-salvaging interventions must address a pattern of changes involving persistent, chronic inflammation and fibrovascular proliferation as key components.