Long-term outcomes of noninfectious uveitis treated with systemic immunomodulatory therapy: a retrospective case series.

OBJECTIVE: To study the clinical characteristics and long-term outcomes of patients with noninfectious uveitis (NIU) who are treated with systemic immunomodulatory therapy (IMT). DESIGN: Retrospective case series. PARTICIPANTS: All consecutive cases of adults with NIU under the care of 5 uveitis subspecialty tertiary care clinics between 2010 to 2021 were included. METHODS: Patient outcomes were assessed at initial presentation and at the latest available follow-up. RESULTS: A total of 418 NIU patients receiving IMT therapy with a median age of 46.0 years and 59.3% female were identified. Each patient required an average of 1.4 agents until achieving an optimal response. Following initial treatment with prednisone, patients were most commonly initiated on methotrexate. The top 3 treatments with the highest proportion of optimal treatment response when taken alone or in combination with other agents were infliximab (79.3%), cyclosporine (75%), and adalimumab (70%). The strongest predictors for requiring a greater number of IMTs trialed were younger age, panuveitis, and a chronic or recurrent disease course. Multivariable linear regression analysis suggested that baseline visual acuity at diagnosis was the only significant predictor of final visual acuity (p < 0.001). CONCLUSIONS: NIU patients on IMT are often trialed on multiple therapeutic agents before achieving an optimal treatment response. Visual acuity at diagnosis is a predictor of final visual outcomes, whereas chronic or recurrent disease course, younger age, and panuveitis are predictors of requiring multiagent treatment regimens.

Characteristics of ocular hypertension and uveitic glaucoma among patients with noninfectious uveitis.

OBJECTIVE: Ocular hypertension and uveitic glaucoma are important downstream sequela of noninfectious uveitis (NIU). Herein, we describe the clinical outcomes of NIU cases with ocular hypertension and uveitic glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: All adults (≥18 years) with NIU under the care of uveitis subspecialty tertiary care clinics between 2010 and 2021 were included. METHODS: The primary outcomes were baseline and final visual acuity. RESULTS: A total of 216 patients out of 914 (23.6%) cases with NIU had ocular hypertension or uveitic glaucoma over the study period. Of all patients with ocular hypertension or uveitic glaucoma, 46% were corticosteroid responders. Baseline and last median visual acuities were better for the ocular hypertension patients compared with patients with uveitic glaucoma (p < 0.001). A higher proportion of patients with uveitic glaucoma than patients with ocular hypertension required glaucoma surgery (p < 0.001). The regression analyses suggested that baseline visual acuity and anatomical classification are significant predictors of last visual acuity, whereas diagnosis of ocular hypertension versus uveitic glaucoma were significant predictors of requirement for glaucoma surgery (p < 0.001). CONCLUSION: A quarter of patients with NIU in this study developed ocular hypertension or uveitic glaucoma. Approximately half of the patients with ocular hypertension or uveitic glaucoma were deemed to be corticosteroid responders. Baseline and last visual acuity outcomes are better amongst ocular hypertension patients compared with those with uveitic glaucoma. Poor baseline visual acuity and panuveitis are predictors of worse vision at last follow-up. Additionally, diagnosis of uveitic glaucoma was a significant predictor of requirement for glaucoma surgery.

Ensemble of deep convolutional neural networks is more accurate and reliable than board-certified ophthalmologists at detecting multiple diseases in retinal fundus photographs.

AIMS: To develop an algorithm to classify multiple retinal pathologies accurately and reliably from fundus photographs and to validate its performance against human experts. METHODS: We trained a deep convolutional ensemble (DCE), an ensemble of five convolutional neural networks (CNNs), to classify retinal fundus photographs into diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and normal eyes. The CNN architecture was based on the InceptionV3 model, and initial weights were pretrained on the ImageNet dataset. We used 43 055 fundus images from 12 public datasets. Five trained ensembles were then tested on an 'unseen' set of 100 images. Seven board-certified ophthalmologists were asked to classify these test images. RESULTS: Board-certified ophthalmologists achieved a mean accuracy of 72.7% over all classes, while the DCE achieved a mean accuracy of 79.2% (p=0.03). The DCE had a statistically significant higher mean F1-score for DR classification compared with the ophthalmologists (76.8% vs 57.5%; p=0.01) and greater but statistically non-significant mean F1-scores for glaucoma (83.9% vs 75.7%; p=0.10), AMD (85.9% vs 85.2%; p=0.69) and normal eyes (73.0% vs 70.5%; p=0.39). The DCE had a greater mean agreement between accuracy and confident of 81.6% vs 70.3% (p<0.001). DISCUSSION: We developed a deep learning model and found that it could more accurately and reliably classify four categories of fundus images compared with board-certified ophthalmologists. This work provides proof-of-principle that an algorithm is capable of accurate and reliable recognition of multiple retinal diseases using only fundus photographs.

Clinical characteristics of non-infectious uveitis treated with and without systemic immunomodulatory therapy.

OBJECTIVE: To compare the patient characteristics and long-term outcomes for those treated with and without systemic immunomodulatory therapy (IMT) for non-infectious uveitis (NIU). DESIGN: Retrospective cohort study. PARTICIPANTS: All consecutive adults with NIU receiving care at 5 uveitis subspecialty tertiary care clinics between 2010 and 2021. METHODS: Clinical outcomes were evaluated on initial presentation and at the last available follow-up. The main outcome measures were baseline characteristics and final visual acuity. RESULTS: A total of 914 NIU patients (418 IMT, 496 non-IMT) with a median age of 51.0 years and 57.4% female were identified. Over half the patients had bilateral disease, with a significantly higher proportion of bilateral cases in the IMT group compared with the non-IMT group (p < 0.001). The IMT group was more likely to have chronic uveitis (p < 0.001), with a higher proportion of patients experiencing cataracts and cystoid macular edema (p < 0.001 for both). A significantly higher proportion of non-IMT patients had anterior uveitis and an idiopathic etiology (p < 0.001). Overall, visual acuity improved significantly from baseline to last follow-up in the entire cohort (p < 0.001), with a slightly better improvement in the IMT group. Multivariable linear regression analysis suggested that baseline visual acuity and panuveitis were significant predictors of final visual acuity (p < 0.001 for both). CONCLUSIONS: NIU patients on IMT are often younger, suffer from bilateral and chronic uveitis, and are more likely to have ocular complications. Those in the non-IMT group are more likely to have anterior idiopathic NIU. Baseline visual acuity and panuveitis are the main predictors of final vision outcomes among patients with NIU.

Refractory Candida dubliniensis Retinitis in an Immunocompetent Patient.

BACKGROUND: Fungal endophthalmitis is an intraocular infection that rarely develops in immunocompetent individuals. CASE: A 35-year-old healthy, immunocompetent male presented with a 1-week history of pain and redness in the left eye. Visual acuity was 20/50. Dilated fundus examination revealed focal chorioretinitis in the posterior pole with associated vitritis, suspicious for a fungal etiology. He was started empirically on oral voriconazole and valacyclovir. A comprehensive systemic workup returned negative. Inflammation worsened and a diagnostic vitrectomy was performed which revealed Candida dubliniensis. The dose of oral voriconazole was increased, and intravitreal voriconazole and amphotericin B injections were added for refractory disease. Treatment response was gauged by fungal pillar height on optical coherence tomography. Eight months of oral voriconazole and 68 intravitreal antifungal injections were required to achieve complete regression and a final visual acuity of 20/20. CONCLUSION: Candida dubliniensis endophthalmitis can affect immunocompetent individuals and require a prolonged treatment course.

Risk Factors for Failure of Tube Shunt Surgery: A Pooled Data Analysis.

PURPOSE: To identify the risk factors associated with failure of tube shunt surgery. DESIGN: Pooled analysis of 3 prospective multicenter, randomized clinical trials. METHODS: A total of 621 patients with medically uncontrolled glaucoma were enrolled, including 276 from the Ahmed Baerveldt Comparison Study, 238 from the Ahmed Versus Baerveldt Study, and 107 from the tube group of the Tube Versus Trabeculectomy Study. Patients were randomized to treatment with an Ahmed glaucoma valve (model FP7) or Baerveldt glaucoma implant (model 101-350). The associations between baseline risk factors and tube shunt failure were assessed using a Cox proportional hazards regression model. The primary outcome measure was the rate of surgical failure defined as intraocular pressure (IOP) > 21 mmHg or reduced < 20% from baseline, IOP ≤ 5 mmHg, loss of light perception vision, reoperation for glaucoma, or removal of implant. RESULTS: The cumulative probability of failure after tube shunt surgery was 38.3% after 5 years. In multivariable analyses, baseline factors that predicted tube shunt failure included preoperative IOP (≤ 21 mmHg compared to IOP > 21 and ≤ 25 mmHg; HR, 2.34; 95% CI, 1.52-3.61; P < .001), neovascular glaucoma (HR, 1.79; 95% CI, 1.28-2.52; P = .001), randomized treatment (for Ahmed glaucoma valve; HR, 1.36; 95% CI, 1.04-1.78; P = .025), and age (for 10 year decrease in age; HR, 1.19; 95% CI, 1.09-1.31; P < .001). CONCLUSIONS: Lower preoperative IOP, neovascular glaucoma, Ahmed implantation, and younger age were predictors of tube shunt failure. This Study provides the largest prospectively collected dataset on tube shunt surgery.

NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY AFTER INTRAVITREAL AFLIBERCEPT FOR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To report a case of nonarteritic anterior ischemic optic neuropathy (NAION) after intravitreal injection in a patient with a history of fellow-eye NAION. METHODS: Observational case report. RESULTS: An 82-year-old woman with a history of fellow eye NAION developed an inferior visual field defect 1 day after an intravitreal aflibercept injection for neovascular age-related macular degeneration. She was found to have optic disk edema and an inferior altitudinal defect, consistent with NAION. The mechanism may have involved compromised perfusion to the optic nerve head related to elevated intraocular pressure or vasoconstriction because of antivascular endothelial growth factor activity. CONCLUSION: Nonarteritic anterior ischemic optic neuropathy is a rare complication of intravitreal injection and may be related to postinjection elevation in intraocular pressure. Monitoring of intraocular pressure postinjection with low-threshold for preinjection aqueous suppression or postinjection anterior chamber paracentesis for persistently elevated intraocular pressure is recommended in patients with a history of NAION.

Bitemporal Hemianopia Secondary to Acute Zonal Occult Outer Retinopathy.

ABSTRACT: A 58-year-old man noticed shadows in the temporal visual field of each eye and photopsias within these scotomas for the past year. Formal visual fields demonstrated bitemporal hemianopia. MRI of the sella was normal, but fundus autofluorescence (FAF) demonstrated an area of hyperautofluorescence in the nasal retina of each eye corresponding to the loss of retinal pigment epithelium and photoreceptors. A diagnosis of acute zonal occult outer retinopathy was made based on the presence of trizonal involvement on FAF. This case is a reminder that bitemporal hemianopia can be caused by a retinopathy involving nasal retina in each eye, and FAF is a very useful test when assessing patients with suspected outer retinal disorders.

10-YEAR FOLLOW-UP OF A SUBCLINICAL CHOROIDAL NEOVASCULAR MEMBRANE IN A PATIENT WITH AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To provide long-term, natural history data of a case of a subclinical choroidal neovascular membrane (CNVM) in the setting of age-related macular degeneration. METHODS: Retrospective review of the 10-year clinical course of a patient including multimodal imaging. RESULTS: A 75-year-old white female with macular degeneration presented with visual acuity of 20/25 in the right eye and 20/40 in the left eye. In the left eye, a retinal pigment epithelial detachment with associated subretinal and intraretinal fluid was found on spectral domain optical coherence tomography. Fluorescein angiography was consistent with a predominately classic CNVM, which was well-visualized on indocyanine green angiography. Treatment was initiated with bevacizumab for 10 months that reduced the amount of subretinal and intraretinal fluid, but progressive geographic atrophy developed over the subsequent 9 years reducing vision to 20/100. Interestingly, at initial presentation, a nonexudative fibrovascular pigment epithelial detachment was detected in the right (contralateral) eye. This was monitored with multimodal imaging twice yearly for 10 years without any signs of exudation, and vision remained 20/25. Optical coherence tomography angiography revealed a remarkably similar appearance of the subclinical CNVM compared with indocyanine green angiography 10 years prior, suggesting anatomical stability. CONCLUSION: The advent of optical coherence tomography angiography has increased the detection of subclinical CNVMs. Recent evidence suggests that subclinical CNVMs have a high rate of progression to exudation over 1 year, which raises the question of whether early treatment is beneficial. This case provides 10-year follow-up with multimodal imaging (fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography) of a subclinical CNVM, which remained stable and without exudation, suggesting that they may be closely observed.

Headache and Bilateral Optic Disc Edema as the Initial Manifestation of Vogt-Koyanagi-Harada Disease.

ABSTRACT: A 31-year-old healthy Asian man presented with new headaches and blurred vision. He was found to have bilateral optic disc edema (ODE) and peripapillary subretinal fluid and was initially investigated for causes of raised intracranial pressure. After referral to neuro-ophthalmology, he received a diagnosis of Vogt-Koyanagi-Harada (VKH) disease and his symptoms, ODE, and vision improved promptly with prednisone treatment. HLA typing was performed and returned positive for the HLA-DRB1*04 subtype. Although VKH disease usually presents with granulomatous uveitis or serous retinal detachments, ODE may manifest early in the disease course. Those with ODE in VKH disease are believed to be older and female, but this case demonstrates that these findings were also seen in a young man.

Incidence of Macular Atrophy after Untreated Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study Report 40.

PURPOSE: To report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy. DESIGN: Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. PARTICIPANTS: Age-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Color fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression. MAIN OUTCOME MEASURES: Incident macular atrophy after nAMD. RESULTS: Of the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3. CONCLUSIONS: The rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Referral characteristics and wait times for uveitis consultation at academic tertiary care centres in Toronto.

OBJECTIVE: To assess the characteristics of referrals to academic uveitis tertiary care centres in Toronto and identify determinants of wait time for consultation. DESIGN: Retrospective case series. METHODS: Consecutive new uveitis referrals received at 5 University of Toronto-affiliated uveitis tertiary care centres, between February 2016 and November 2016, were included. RESULTS: A total of 159 new uveitis referrals were received from academic (69%) and community (31%) providers. A large proportion of referrals were sent by comprehensive ophthalmologists (33%) and retina specialists (38%). Disease was bilateral in 46% of cases, had an acute onset in 43% of cases, and was classified as posterior uveitis in 38% of cases. Disease etiology at the time of referral was unknown in 55% of cases. Only 43% of all referrals included a basic uveitis workup, and patients who had undergone diagnostic testing had a shorter wait time for consultation (41 ± 43 vs. 59 ± 54 days, p = 0.033). Acute uveitis had a shorter wait time compared with recurrent and chronic uveitis (33 ± 42 vs. 66 ± 44 and 59 ± 58 days, p < 0.001). Referrals triaged as urgent had significantly shorter wait times compared with referrals triaged as semiurgent or elective (7 ± 10 vs. 54 ± 43 and 88 ± 59, p < 0.001). CONCLUSIONS: Referrals to academic uveitis tertiary care centres in Toronto are often acute, bilateral cases affecting the posterior segment without a known etiology. Approximately half of referrals include no diagnostic workup, which may delay diagnosis for patients and lengthen wait times for consultation. We provide a set of recommendations for investigations that should be included in uveitis referrals.

Comparison of the Ahmed and Baerveldt glaucoma shunts with combined cataract extraction.

OBJECTIVE: To compare the surgical outcomes of combined phacoemulsification with either Ahmed glaucoma valve (AGV) or Baerveldt glaucoma implant (BGI). DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 104 eyes that underwent combined phacoemulsification with either AGV (PhacoAGV; n = 57) or BGI (PhacoBGI; n = 47) implantation. METHODS: Failure was defined as uncontrolled intraocular pressure (IOP; <5 mm Hg, ≥18 mm Hg, or <20% reduction), additional glaucoma surgery, vision-threatening complications, or progression to no-light-perception vision. RESULTS: The PhacoAGV group was older (p = 0.03), had poorer baseline visual acuity (VA; p = 0.001), and had fewer previous glaucoma surgeries (p = 0.04). Both groups had similar baseline IOP (PhacoAGV: 26.4 ± 8.3 mm Hg; PhacoBGI: 25.7 ± 7.3; p = 0.66) and glaucoma medications (PhacoAGV: 3.8 ± 1.0; PhacoBGI: 3.6 ± 1.5; p = 0.54). At 2 years, failure rates were 44% in the PhacoAGV group and 23% in the PhacoBGI group (p = 0.02). Both groups had similar mean IOP reduction (PhacoAGV: 45%; PhacoBGI: 47%, p = 0.67) and medication use reduction (PhacoAGV: 47%; PhacoBGI: 58%, p = 0.38). The PhacoBGI group had higher IOP and medication use up to 1 month (p < 0.05). Both groups improved in VA from baseline (p < 0.05) and had similar overall complication rates (p = 0.31). The PhacoBGI group required more overall interventions (p < 0.0005). CONCLUSIONS: This comparative study found no difference in IOP, glaucoma medications, or complication rates between PhacoAGV and PhacoBGI at 2 years, despite BGIs being implanted in patients at higher risk for failure. The PhacoAGV group had higher failure rates at 2 years. Both groups had significant improvements in VA due to removal of their cataracts. The PhacoBGI group required more interventions, but most of these were minor slit-lamp procedures.