Severe Occlusive Retinal Vasculitis in an Immunocompetent Patient with Chronic CMV Anterior Uveitis.

PURPOSE: We report a unique case of non-necrotizing occlusive retinal vasculitis presenting two years following chronic hypertensive uveitis. METHODS: Case Report. RESULTS: A 32-year-old Iraqi woman with a history of Posner-Schlossman Syndrome diagnosed 10 years prior presented with blurred vision and redness in her left eye. Examination demonstrated ocular hypertension, keratic precipitates, and inflammatory cells in the anterior chamber. Quantitative real-time PCR confirmed the presence of cytomegalovirus in the aqueous humor, and dilated posterior segment examination was negative for any signs of intraocular inflammation, retinitis, or vasculitis. Her uveitis workup was otherwise negative, and she was treated with valganciclovir for 6 months. Two years after her initial presentation, she was noted to have a new vitreous hemorrhage in the left eye. Fluorescein angiography demonstrated an occlusive retinal vasculitis with extensive neovascularization without retinitis. Quantitative real-time PCR again demonstrated the presence of cytomegalovirus in the anterior chamber. Her uveitis workup was repeated, which has now returned positive for HLA-B51. She otherwise did not demonstrate any systemic signs of Behcet's Disease. She was restarted on valganciclovir and oral prednisone and referred to rheumatology for consideration of adalimumab initiation. Thus far she has responded very well to treatment. CONCLUSION: This case highlights the importance of serial posterior segment examinations and HLA-B51 testing in individuals with cytomegalovirus anterior uveitis.

Chorioretinopathy presenting as bitemporal hemianopia.

INTRODUCTION: Bitemporal hemianopia is usually caused by chiasmal pathology. Rarely, chorioretinal lesions may develop symmetrically in both eyes and mimic chiasmopathy. METHODS: This case series included three patients who presented to a tertiary neuro-ophthalmology centre with bitemporal hemianopic defects between 2021 and 2023 and were subsequently diagnosed with bilateral chorioretinopathy. All patients received comprehensive examinations from a fellowship-trained neuro-ophthalmologist and uveitis specialist to rule out other causes of visual dysfunction. RESULTS: Three males aged 64, 62, and 72 years were included. All patients showed bitemporal hemianopic defects crossing the vertical midline on automated perimetry and binasal thinning of the macular ganglion cell complex on spectral-domain optical coherence tomography (OCT). Fundus autofluorescence (FAF) showed classical features of acute zonal occult outer retinopathy (AZOOR) in two patients and central serous chorioretinopathy (CSCR) in another. AZOOR diagnosis was preceded by neuroimaging in both cases, whereas the patient with CSCR had longstanding, electroretinography-confirmed lesions and did not require neuroimaging. Fundus appearance and visual field defects remained stable in all patients across 3-6 months of follow-up. CONCLUSIONS: Bilateral chorioretinopathy should be considered in the differential diagnosis of bitemporal hemianopia in specific cases, including when visual field defects cross the vertical midline and when neuroimaging fails to reveal chiasmal pathology. FAF and macular OCT have high diagnostic yield as initial investigations.

Anterior uveitis for the comprehensive ophthalmologist.

Anterior uveitis presents a diagnostic challenge due to its wide array of etiologies and clinical manifestations. This narrative review aims to equip general ophthalmologists with a comprehensive understanding of anterior uveitis epidemiology, diagnosis, and treatment. Particular emphasis is placed on developing a tailored and stepwise strategy, rather than a one-size-fits-all approach, for the workup and treatment of anterior uveitis. Chest radiography and serologic testing for syphilis, human leukocyte antigen B27, and angiotensin-converting enzyme are appropriate routine investigations in cases of severe, bilateral, recurrent, or chronic anterior uveitis. Additional testing should be guided by clinical findings and regional epidemiology, especially when considering expensive and invasive modalities. Investigations that are obtained in the absence of clinical and epidemiologic orientation are of limited utility and incur significant costs to patients and health care systems. Most cases of anatomically isolated anterior uveitis resolve with topical corticosteroids, but some patients require escalation to systemic immunomodulatory therapy (IMT). IMT should be considered in patients who respond poorly to corticosteroids, develop side effects related to corticosteroids that limit their use, require high doses to maintain disease remission, or have concomitant systemic inflammatory disease. Comprehensive ophthalmologists should feel comfortable comanaging patients that require conventional disease-modifying antirheumatic drugs/antimetabolite therapy (i.e., methotrexate, azathioprine, and mycophenolate mofetil) with rheumatologists and providing guidance on ocular dosing. When uveitis quiescence cannot be achieved despite maximally tolerated antimetabolite therapy, patients should be referred to a uveitis specialist for consultation and consideration of IMT escalation. The timing of uveitis referral may depend on local factors specific to health care jurisdictions.

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.

Antiviral therapy defiant mixed viral retinitis post hematopoietic allogeneic stem cell transplant.

Cytomegalovirus (CMV) retinitis is an uncommon presentation post allogeneic transplant and can be vision-threatening. Our case demonstrates the occurrence of polymerase chain reaction (PCR) proven mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogeneic stem cell transplant despite multiple prophylactic antiviral therapies, including letermovir, and in the documented absence of CMV DNAemia. A 21-year-old female with acute myeloid leukemia presented with mixed viral retinitis (cytomegalovirus and varicella zoster virus) post allogenic transplant. This presentation occurred despite ongoing standard prophylaxis for both of these viruses, as well as following two courses of treatment for CMV viremia, with a documented negative CMV PCR in the blood prior to the presentation with retinitis. The patient was treated with intravenous ganciclovir and subsequently transitioned to oral valganciclovir with durable resolution of the retinitis. We report a rare case of mixed viral retinitis occurring despite multiple antiviral prophylaxes including letermovir and with PCR-documented absence of preceding CMV viremia, in a post-allogeneic stem cell transplant patient, with PCR of the aqueous fluid demonstrating two viral populations. With very little existing literature on either mixed viral retinitis or CMV retinitis during letermovir prophylaxis, this case expands the literature on both topics. CMV retinitis is an uncommon potentially vision threatening presentation post hematopoietic stem cell transplant, and can occur due to early CMV reactivation, low CD4 count, and delayed CD4 lymphocyte recovery. Letermovir has poor CNS and retinal penetration. This case highlights the need for more research on secondary prophylaxis with letermovir.

Initial anterior uveitis event associated with recent novel SARS-CoV-2 (COVID-19) infection in the setting of HLA-B27.

Purpose: To describe an atypical ocular manifestation following SARS-CoV-2 infection. Observations: A 27-year old previously healthy male with no past ocular history presented with pain, photophobia and red eye in his left eye (OS). His only notable mention on review of systems was a positive SARS-CoV-2 infection three weeks prior. Slit lamp examination demonstrated fine inferior keratic precipitates (KPs) in the inferior cornea and 3+ anterior chamber cells OS. There was no vitritis or chorioretinal lesions. The patient was diagnosed with his first event of acute anterior uveitis. Standard ocular inflammatory panel returned positive for HLA-B27. The postulated mechanism of initial anterior uveitis attack in the setting of COVID-19 infection was dysregulation of inflammatory cells and mediators in a patient with baseline elevated risk for ocular inflammation. Conclusions and Importance: It is crucial to investigate patients for HLA-B27 following initial anterior uveitis event if infected by SARS-CoV-2, as patients with HLA-B27 are at baseline higher risk of ocular inflammatory dysregulation.

Vogt-Koyanagi-Harada disease following influenza vaccination.

Purpose: To report a case of Vogt-Koyanagi-Harada (VKH) disease following influenza vaccination. Observations: A 30-year-old Filipino male developed bilateral pain, redness, photophobia, floaters, headache and tinnitus 2 days after receiving the annual influenza vaccine. He presented to the emergency department 5 days after symptom onset. His past medical and ocular history was unremarkable. His best-corrected distance visual acuity (BCVA) was 20/100 in the right eye (OD) and 20/150 in the left eye (OS). Slit-lamp examination revealed fine keratic precipitates and 1+ anterior chamber cells in both eyes (OU). Dilated fundus examination revealed 1+ vitreous cells with trace haze and multiple serous retinal detachments OU. Magnetic resonance imaging (MRI) of the brain and chest X-ray were unremarkable. Serologic testing was negative for infectious, inflammatory and neoplastic causes. The patient tested positive for HLA-DR4. A diagnosis of acute Vogt-Koyanagi-Harada disease was made and high-dose oral prednisone, intravitreal triamcinolone acetonide and mycophenolate mofetil were needed to achieve quiescence. At 6 months follow-up, our patient remains in remission with no active intraocular inflammation or subretinal fluid. His BCVA has improved to 20/50 OD and 20/30 OS. Conclusion and importance: The annual influenza vaccine may be a trigger for onset or recurrence of VKH in genetically susceptible individuals.

Monocular Temporal Hemianopia due to Acute Zonal Occult Outer Retinopathy.

Retinal disease may mimic an optic neuropathy since both may result in a relative afferent pupillary defect (RAPD), and retinal abnormalities may not be evident on a clinical exam. We report a case of a young woman with a monocular temporal hemianopia respecting the vertical meridian due to acute zonal occult outer retinopathy (AZOOR). This 34-year-old woman presented with a 10-day history of left eye vision loss and was found to have a visual acuity of 20/20 in both eyes, a left RAPD, and left temporal hemianopia on Humphrey 24-2 SITA-Fast visual field testing. Dilated fundus examination showed a normal-appearing optic nerve and retina in both eyes. She had already had a normal magnetic resonance imaging of the orbits with contrast and retinal disease was suspected. Optical coherence tomography showed dropout of the ellipsoid zone in the peripapillary retina, and fundus autofluorescence showed hyper-autoflourescence in the peripapillary region of the left eye. A diagnosis of AZOOR was made, and no improvement with prednisone occurred at final follow-up. This case demonstrates the importance of multimodal imaging in patients referred for optic neuropathies since retinal disease such as AZOOR can produce visual field defects characteristic of optic nerve disease.

TATTOO-ASSOCIATED CASES OF POSTERIOR SEGMENT UVEITIS WITH VOGT-KOYANAGI-HARADA DISEASE-LIKE FEATURES.

PURPOSE: To present two patients with treatment-naïve posterior segment uveitis with Vogt-Koyanagi-Harada-like features associated with tattoo-related inflammatory skin changes. METHODS: Retrospective report of two cases. RESULTS: Using clinical history and multimodal imaging, a diagnosis of posterior segment uveitis with Vogt-Koyanagi-Harada-like features was made in association with tattoo skin changes in both patients. CONCLUSION: Physicians should be aware that tattoo-associated posterior segment uveitis with Vogt-Koyanagi-Harada-like features can occur.

Incidence of very high defibrillation thresholds (DFT) and efficacy of subcutaneous (SQ) array insertion during implantable cardioverter defibrillator (ICD) implantation.

BACKGROUND: The incidence, risk factors, and management of very high defibrillation thresholds (DFTs) during present-day implantable cardioverter defibrillator (ICD) testing are not well known. OBJECTIVES: The purpose of this study was to assess (1) the incidence of very high DFTs and (2) the efficacy/safety of routinely adding a subcutaneous (SQ) array for these patients. METHODS: The study evaluated patients undergoing first-time ICD implantation at Southlake Regional Healthcare Centre from January 2006 to December 2007. All implanted ICDs had a maximal output of 35 J. Patients with DFTs greater than a 10-J safety margin from maximum output were considered to have very high readings and underwent SQ array insertion after other attempts at lowering DFT (group I). These patients were compared with the rest of the patients who had acceptable DFTs (group II) using both univariate and multivariate logistic regression analysis. Outcomes of array insertion were also assessed. RESULTS: A total of 313 patients underwent first-time ICD implantation during the analysis period. Of those, 16 (5.1%) had very high DFTs (group I). By univariate analysis, advanced New York Heart Association class (3 or 4), congestive heart failure hospitalization, non-ischemic cardiomyopathy, amiodarone use, implant of a biventricular device, and highest quartile of left ventricular (LV) chamber enlargement were all significant predictors of very high DFTs (p < 0.05). By multivariate analysis, only amiodarone use [odds ratio (OR) = 10.3, 95% confidence interval (95% CI) = 3.7-32.6] and being in the highest quartile for LV diastolic diameter [OR = 5.4, 95% CI = 1.4-20.8] predicted very high DFT. In all 16 cases, other methods to lower DFT prior to array insertion were attempted but failed for all patients: reversing shock polarity (n = 15), removing the superior vena cava coil (n = 14), reprogramming shock waveform (n = 9), and repositioning right ventricular lead (n = 9). Addition of the array successfully decreased DFT to within safety margin for all patients (33 ± 2 vs 21 ± 5 J, p = 0.02). Complication due to array insertion occurred in one patient (pneumothorax). CONCLUSIONS: Very high DFTs occur in about 5% of patients undergoing ICD implantation and may be predicted by LV dilation and amiodarone use. SQ array insertion reliably corrects this problem over other interventions with a low rate of procedural complication.

Predictors of appropriate implantable cardioverter defibrillator (ICD) therapy in primary prevention patients with ischemic and nonischemic cardiomyopathy.

BACKGROUND: We sought to assess predictors of appropriate implantable cardioverter defibrillator (ICD) therapy in patients receiving primary prevention ICDs. METHODS: Four hundred twenty-one consecutive patients (ischemic and nonischemic) undergoing primary prevention ICD implantation were studied. Patients were grouped based on the presence/absence of appropriate ICD therapy. Summary data and stored electrograms from ICDs were reviewed to determine appropriateness of therapy. Predictors of therapy were assessed by both univariate and multivariate Cox regression analysis. RESULTS: Of 421 primary prevention patients undergoing ICD implantation, 79 (19%) had received appropriate ICD therapies. By univariate comparison, nonsustained ventricular tachycardia (NSVT), male sex, left ventricle diastolic diameter (LVDD), and hypertension were all significant predictors for ICD therapy over a mean follow-up time of 751 +/- 493 days (P