Endophthalmitis in Eyes Treated with the Port Delivery System with Ranibizumab: Summary of Cases during Clinical Trial Development.

PURPOSE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration. The United States Prescribing Information has a Boxed Warning for endophthalmitis and reports the incidence rate in patients developing endophthalmitis after receiving the PDS compared with monthly intravitreal ranibizumab. Endophthalmitis cases noted in the Boxed Warning, treatment outcomes, potential contributing factors, and potential mitigations are summarized. DESIGN: Retrospective review of endophthalmitis cases in PDS-treated patients in the phase II Ladder (NCT02510794) and phase III Archway (NCT03677934) and Portal (NCT03683251) trials. PARTICIPANTS: Endophthalmitis cases in the pooled all-PDS safety population (N = 555) including PDS patients in Ladder, Archway, or Portal. METHODS: Ladder patients received PDS (10, 40, or 100 mg/ml) with pro re nata refill-exchanges. Archway patients received PDS 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W). Portal patients received PDS Q24W from day 1. MAIN OUTCOME MEASURES: Clinical features, management, and visual outcomes were summarized. Cases were summarized by date of PDS implant and/or refill, other prior invasive procedures/refills, and preceding/concurrent conjunctival complications. RESULTS: Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021. All were cultured (3 were culture positive) and treated with intravitreal antibiotics. Two cases (2/555 [0.4%]) occurred in the immediate postoperative period (days 5 and 6). Nine cases occurred later (day range: 57-853), including 4 before the first refill-exchange (day range: 57-161). Five patients received between 1 and 11 refill-exchanges before the event (onset: 6-168 days after last refill-exchange). Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or ≥20/40; 4 patients experienced vision loss of ≥15 ETDRS letters. CONCLUSIONS: Endophthalmitis is a serious complication that can endanger vision after any ocular procedure, including PDS implantation. Most, but not all, of this limited series of endophthalmitis cases were late onset, associated with conjunctival breach, and recovered vision with treatment. Meticulous attention to PDS surgical techniques with vigilant monitoring of conjunctiva during follow-up may minimize risk of endophthalmitis. Prompt treatment is critical for optimizing patient outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Primary Autologous Stem Cell Transplantation for Unilateral Primary Central Nervous System Lymphoma-Ophthalmic Variant (Primary Vitreoretinal Lymphoma).

Purpose: To describe the long-term outcomes of 2 cases of primary autologous stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma-ophthalmic variant (PCNSL-O) or primary vitreoretinal lymphoma (PVRL). Methods: Two cases and their findings were analyzed. A review of the histopathology, systemic treatment, and multimodal ocular imaging was performed. Results: A 52-year-old woman and 56-year-old woman were referred for vitritis and retinal lesions suspicious for PCNSL-O. The initial vitreous biopsies were inconclusive. Both patients had subsequent chorioretinal biopsies that confirmed the diagnosis of diffuse large B-cell lymphoma. No systemic or central nervous system involvement was found on systemic workup. Both patients received intravitreal and systemic chemotherapy followed by ASCT, and both remained in complete remission 7 and 8 years later. Conclusions: These cases show the long-term survival of patients diagnosed with PVRL when primary ASCT, the primary treatment for PCNSL, is performed.

Ocular Toxoplasmosis: No Stranger to the Masquerade Ball.

Purpose: This article illustrates multiple atypical manifestations of ocular toxoplasmosis masquerading as acute retinal necrosis and vitreoretinal lymphoma. Methods: Two case presentations are discussed, and the body of pertinent literature is reviewed and discussed. Results: In these cases, an extensive workup and attention to history lead to the correct diagnosis and management. Conclusions: Aggressive cases of ocular toxoplasmosis may present in a variety of phenotypes that may mimic other vision- and potentially life-threatening conditions, particularly in a milieu of inadequate endogenous and exogenous antimicrobial defenses.

Clinical Practice Update: Management of Infectious Endophthalmitis After Intravitreal Anti-VEGF Injection.

Although infectious endophthalmitis after intravitreal antivascular endothelial growth factor injections is rare, it is the most feared and potentially devastating complication of this procedure. There is no high-level evidence to provide definitive guidance on the management of endophthalmitis occurring after intravitreal injection (IVI). This clinical practice update reviews the published literature regarding post-IVI endophthalmitis and highlights areas in which further research is needed to better guide its management.

RETINAL DETACHMENT IN EYES WITH BOSTON TYPE 1 KERATOPROSTHESIS: Surgical Techniques and Mid-Term Outcomes.

PURPOSE: To evaluate the mid-term outcomes of pars plana vitrectomy performed for retinal detachment (RD) repair after Boston Type 1 keratoprosthesis (KPro) implantation. METHODS: Retrospective review of medical records of KPro implanted at the Stein Eye Institute presenting with RD and treated by pars plana vitrectomy. Functional success was defined as a postoperative visual acuity maintained within 2 Snellen lines of the corrected distance visual acuity measured before the development of the RD (baseline) and anatomical success as an attached retina after the pars plana vitrectomy. Kaplan-Meyer survival analyses were performed. RESULTS: Among the 224 KPro performed, 28 (15.2%) RD were identified; of which, 21 (9.4%) were included. The mean follow-up was 42.5 ± 27.3 months. Vitreoretinal proliferation was present in 18 of 21 eyes (85.7%). Surgical techniques were adapted to the complex anterior segment anatomy of KPro eyes. Anatomical success was achieved in 18 of 21 eyes (85.7%). Functional success occurred in 17 of 21 eyes (81.0%), and 5 of 21 eyes (23.8%) reached 20/400 or better visual acuity at the final follow-up. The KPro was retained in 11 in 21 eyes (52.4%). The retention rate decreased from 94.7% at 1 year to 53.5% at 5 years. The most frequent complications were retroprosthetic membrane (47.6%) and corneal melt (23.8%). CONCLUSION: Modified pars plana vitrectomy techniques resulted in relatively good mid-term anatomical, functional, and retention rate outcomes, given the severity of RD at presentation and the numerous preoperative comorbidities of KPro eyes.

Prospective, Randomized Trial Comparing Simulator-based versus Traditional Teaching of Direct Ophthalmoscopy for Medical Students.

OBJECTIVE: To compare results of simulator-based vs traditional training of medical students in direct ophthalmoscopy. DESIGN: Randomized controlled trial. METHODS: First-year medical student volunteers completed 1 hour of didactic instruction regarding direct ophthalmoscopes, fundus anatomy, and signs of disease. Students were randomized to an additional hour of training on a direct ophthalmoscope simulator (n = 17) or supervised practice examining classmates (traditional method, n = 16). After 1 week of independent student practice using assigned training methods, masked ophthalmologist observers assessed student ophthalmoscopy skills (technique, efficiency, and global performance) during examination of 5 patient volunteers, using 5-point Likert scales. Students recorded findings and lesion location for each patient. Two masked ophthalmologists graded answer sheets independently using 3-point scales. Students completed surveys before randomization and after assessments. Training groups were compared for grades, observer- and patient-assigned scores, and survey responses. RESULTS: The simulator group reported longer practice times than the traditional group (P = .002). Observers assigned higher technique scores to the simulator group after adjustment for practice time (P = .034). Combined grades (maximum points = 20) were higher for the simulator group (median: 5.0, range: 0.0-11.0) than for the traditional group (median: 4.0, range: 0.0-9.0), although the difference was not significant. The simulator group was less likely to mistake the location of a macular scar in 1 patient (odds ratio: 0.28, 95% confidence interval: 0.056-1.35, P = .013). CONCLUSIONS: Direct ophthalmoscopy is difficult, regardless of training technique, but simulator-based training has apparent advantages, including improved technique, the ability to localize fundus lesions, and a fostering of interest in learning ophthalmoscopy, reflected by increased practice time.

Glaucoma After Iodine-125 Brachytherapy for Uveal Melanoma: Incidence and Risk Factors.

PRéCIS:: A single-center retrospective review over a 10-year period discovered an 8.6% risk of developing secondary open-angle glaucoma, and a 6.7% risk of neovascular glaucoma after brachytherapy for uveal melanoma. Additional risk factors were identified. PURPOSE: To report the incidence and identify risk factors for secondary open-angle glaucoma and neovascular glaucoma after iodine-125 brachytherapy for uveal melanoma in a tertiary ocular oncology and glaucoma practice. PATIENTS AND METHODS: Eyes of patients who had been diagnosed and treated with iodine-12 brachytherapy for uveal melanoma over a 10-year period were included for review. Secondary open-angle glaucoma was defined as meeting the following criteria: at least 3 measurements of intraocular pressure (IOP) ≥21 mm Hg after the removal of the iodine-125 plaque and an open angle on gonioscopy. Neovascular glaucoma was defined as meeting the following criteria: at least 3 measurements of IOP ≥21 mm Hg and neovascularization of the iris or anterior chamber angle. Cumulative incidence was calculated and survival analysis was used to analyze risk factors for both secondary open-angle glaucoma and neovascular glaucoma. RESULTS: A total of 374 eyes in patients diagnosed with uveal melanoma and treated with Iodine-125 brachytherapy were included in the study. Thirty-one eyes (8.6%) were diagnosed with secondary open-angle glaucoma and 25 eyes (6.7%) were diagnosed with neovascular glaucoma. Multivariate analysis identified the following risk factors for secondary open-angle glaucoma: older age, greater tumor size, iris location of uveal melanoma, higher baseline IOP, ciliary body involvement, and eyes having undergone combined brachytherapy with vitrectomy and silicone oil placement for radiation attenuation. The risk factors for neovascular glaucoma were as follows: greater tumor size, greater number of pack-years smoking history, pseudophakia, and higher grade of radiation retinopathy severity by fluorescein angiogram. CONCLUSIONS: We have identified additional risk factors for the development of both secondary open-angle glaucoma and neovascular glaucoma in patients with uveal melanoma who have undergone iodine-125 brachytherapy for local tumor control. The risk of secondary glaucoma is substantial. Close ophthalmic monitoring of patients is necessary for detection and timely treatment of glaucoma to maximize visual outcome.

Clinic-based ultra-wide field retinal imaging in a pediatric population.

BACKGROUND: Pediatric retinal disorders, although uncommon, can be challenging to assess in the clinic setting and often requires an exam under anesthesia. The purpose of our study was to evaluate the use of ultra-wide field retinal imaging in children without sedation in an outpatient clinic. METHODS: We performed a retrospective case series of patients 18 years or younger who received ultra-wide field imaging over a one year period. The age, gender, and clinical course were documented. Color fundus and red-free images were reviewed to assess field of view. Ultra-wide field autofluorescence (UWF-FAF) was evaluated for abnormal autofluorescence patterns and ultra-wide field fluorescein angiography (UWF-FA) was assessed for angiographic phase and field of view. RESULTS: A total of 107 eyes of 55 patients with a mean age of 11.1 years (SD 3.7 years, range 3-18 years) were evaluated. Twenty-seven (49%) patients were male. The most common diagnosis was retinopathy of prematurity (7 of 55 patients, 12.7%) followed by trauma (7.4%), Coats disease (7.4%), and rhegmatogenous retinal detachment (7.4%). The number of quadrants visualized anterior to the equator correlated with patient age (r = 0.4, p < 0.01). On UWF-FA, 6 of 14 patients (43%) had images of the arterial phase captured and 14 of 14 patients (100%) had images of the venous phase or later captured. CONCLUSIONS: We demonstrated that UWF imaging is obtainable in children as young as 3 years old without sedation. UWF fundus photography, UWF-FAF and UWF-FA were useful clinical adjuvants to examination and provide additional information for documenting and monitoring pediatric retinal diseases.

Adoption of Electronic Health Records and Perceptions of Financial and Clinical Outcomes Among Ophthalmologists in the United States.

Importance: Assessing the rate of electronic health record (EHR) adoption and ophthalmologists' perceptions on financial and clinical productivity is important in understanding how to direct future design and health care policy. Objective: To assess adoption rate and perceptions of financial and clinical outcomes of EHRs among ophthalmologists in the United States. Design, Setting, and Participants: Population-based, cross-sectional study. A random sample of 2000 ophthalmologists was generated on the basis of mailing address zip codes from the 2015 American Academy of Ophthalmology US active membership database, which included more than 18 000 ophthalmologists. A survey was sent by email to assess adoption rate of EHRs, perceptions of financial and clinical productivity, and engagement with Medicare and Medicaid programs that incentivize the use of EHRs. The survey was conducted between 2015 and 2016. Main Outcomes and Measures: Adoption rate of EHRs and perceptions of financial and clinical productivity. Results: The adoption rate of EHRs among surveyed ophthalmologists (348 respondents) was 72.1%. The responding ophthalmologists perceived that their net revenues and productivity have declined and that practice costs are higher with EHR use. Of those who attested for stage 1 of the EHR incentive program, 83% had already or were planning to attest to stage 2, but 9% had no plans. Conclusions and Relevance: The adoption of EHRs by ophthalmologists has more than doubled since a 2011 survey and is similar to that of primary care physicians (79%). In comparison with 2 previous surveys of ophthalmologists, respondents had more negative perceptions of EHR productivity outcomes and effect on practice costs, although financial data were not collected in this survey to support these opinions. These negative perceptions suggest that more attention should be placed on improving the efficiency and usability of EHR systems.

EARLY DETECTION OF RETINAL HEMANGIOBLASTOMAS IN VON HIPPEL-LINDAU DISEASE USING ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY.

PURPOSE: To study the use of ultra-widefield fluorescein angiography (UWF FA) in the detection and management of retinal capillary hemangioblastomas in patients with von Hippel-Lindau disease. METHODS: This is a retrospective study of patients with von Hippel-Lindau disease who underwent UWF FA using the Optos camera at a single center from June 2009 to May 2015. The clinical use of UWF FA was reviewed, and the number of hemangioblastomas identified on UWF FA was compared with ophthalmoscopy and a simulated seven standard field (7SF) FA montage. RESULTS: Twenty eyes of 10 patients were identified. Only 33% of lesions seen on UWF FA were also found on ophthalmoscopy, and 88% of lesions visualized on UWF FA were located outside the 7SF overlay. In 5 eyes that had gaze steering, 18% of lesions could be visualized only on gaze-steered images. For the 14 eyes with data available, 6 had procedures recommended and 8 eyes observed based on data from UWF FA. One of 20 eyes had a lesion on ophthalmoscopy that was missed by imaging. CONCLUSION: Ultra-widefield FA using the Optos camera is helpful for the evaluation and management of patients with von Hippel-Lindau disease. The UWF FA with gaze steering appears to detect more hemangioblastomas than ophthalmoscopy and conventional angiography.

NEW ULTRA-WIDE-FIELD ANGIOGRAPHIC GRADING SCHEME FOR RADIATION RETINOPATHY AFTER IODINE-125 BRACHYTHERAPY FOR UVEAL MELANOMA.

PURPOSE: Radiation retinopathy remains incompletely characterized and may cause severe vision loss. Ultra-wide-field fluorescein angiography provides a pan-fundus view of vascular alterations caused by radiation treatment and may predict visual and ocular outcomes. We have developed a grading scheme to describe pan-fundus severity and to predict the progression of radiation retinopathy in patients treated for uveal melanoma with iodine-125 brachytherapy. METHODS: A retrospective review of patients treated with standard iodine-125 brachytherapy for uveal melanoma at the Ophthalmic Oncology Center at the University of California, Los Angeles, who had undergone both baseline and postbrachytherapy ultra-wide-field fluorescein angiography. A grading scheme was devised based on observations of vascular leakage, retinal perfusion status, and retinal proliferation. The correlation of grade severity with patient characteristics, tumor features, visual acuity, optical coherence tomography findings, and neovascular glaucoma was measured with chi-square and one-way analysis of variance analyses. RESULTS: Sixty-seven patients were identified for review. Consistent wide-field angiographic patterns after brachytherapy were observed and graded as follows: Grade 0: normal; Grade 1: late foveal leakage; Grade 2: late peripheral leakage; Grade 3: presence of nonperfusion; and Grade 4: retinal neovascularization. Six eyes (8.9%) were Grade 0; 16 (23.8%) were Grade 1; 25 (37.3%) were Grade 2; 16 (23.4%) were Grade 3; and 4 (6.0%) were Grade 4. Higher grade radiation severity correlated significantly with duration of follow-up (P < 0.02); younger age (P = 0.035); worse visual acuity (P = 0.001); cystoid macular edema or atrophy on optical coherence tomography (P < 0.0001); and neovascular glaucoma (P = 0.003). CONCLUSION: Wide-field fluorescein angiography revealed distinct fundus-wide patterns of vascular damage, which were progressive in nature in eyes treated with iodine-125 brachytherapy for uveal melanoma and correlated with signs of progressive vascular injury. This grading scheme may have prognostic value to predict the progression of radiation retinopathy and to prognosticate visual outcomes in patients undergoing brachytherapy.

Continuous Curvilinear Capsulorhexis Training and Non-Rhexis Related Vitreous Loss: The Specificity of Virtual Reality Simulator Surgical Training (An American Ophthalmological Society Thesis).

PURPOSE: To assess the specificity of simulation-based virtual reality ophthalmic cataract surgery training on the Eyesi ophthalmic virtual reality surgical simulator, and test the hypothesis that microsurgical motor learning is highly specific. METHODS: Retrospective educational interventional case series. The rates of vitreous loss and retained lens material, and vitreous loss and retained lens material associated with an errant continuous curvilinear capsulorhexis (CCC) were assessed among 1037 consecutive cataract surgeries performed during four consecutive academic years at a teaching hospital. The data were grouped by Eyesi use and capsulorhexis intensive training curriculum (CITC) completion. The main intervention was the completion of the CITC on the Eyesi. RESULTS: In the Eyesi simulator experience-based stratification, the vitreous loss rate was similar in each group (chi square p=0.95) and was not preceded by an errant CCC in 86.2% for "CITC done at least once", 57.1% for "CITC not done, but some Eyesi use", and 48.9% for "none" training groups (p=4×10-5). Retained lens material overall and occurring among the errant CCC cases was similar among training groups (p=0.82 and p=0.71, respectively). CONCLUSIONS: Eyesi capsulorhexis training was not associated with lower vitreous loss rates overall. However, non-errant CCC associated vitreous loss was higher among those who underwent Eyesi capsulorhexis training. Training focused on the CCC portion of cataract surgery may not reduce vitreous loss unassociated with an errant CCC. It is likely that surgical training is highly specific to the task being trained. Residents may need to be trained for all surgical steps with adequate intensity to minimize overall complication rates.

RESOLUTION OF TREATMENT-RESISTANT SUBRETINAL FLUID IN A PATIENT WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION FOLLOWING ENDOPHTHALMITIS.

PURPOSE: This is the first report to the best of the authors' knowledge to show resolution of subretinal fluid and treatment requirement in a case of exudative age-related macular degeneration (eAMD) with persistent fluid despite treatment that resolved following an episode of culture-positive bacterial endophthalmitis. METHODS: A 73-year-old man with history of eAMD of the right eye presented with acute postinjection bacterial endophthalmitis 3 days after injection. He had a history of only partially treatment-responsive eAMD that had been treated over a period of 8 years. RESULTS: After tap-and-inject treatment of endophthalmitis with ceftazidime, vancomycin, and dexamethasone, the patient returned for follow-up with visual improvement and resolution of the subretinal fluid. The previously treatment-resistant eAMD remains quiescent without further treatment after 10 months of follow-up. CONCLUSION: It is possible that some aspect of the infection, inflammation, or treatment of endophthalmitis had a disease-modifying impact on the eAMD. Further research into the components of endophthalmitis and its treatment may result in the discovery of new treatment approaches or treatment targets.