Logistic Regression Classification of Primary Vitreoretinal Lymphoma versus Uveitis by Interleukin 6 and Interleukin 10 Levels.

PURPOSE: To assess the diagnostic performance and generalizability of logistic regression in classifying primary vitreoretinal lymphoma (PVRL) versus uveitis from intraocular cytokine levels in a single-center retrospective cohort, comparing a logistic regression model and previously published Interleukin Score for Intraocular Lymphoma Diagnosis (ISOLD) scores against the interleukin 10 (IL-10)-to-interleukin 6 (IL-6) ratio. DESIGN: Retrospective cohort study. PARTICIPANTS: Patient histories, pathology reports, and intraocular cytokine levels from 2339 patient entries in the National Eye Institute Histopathology Core database. METHODS: Patient diagnoses of PVRL versus uveitis and associated aqueous or vitreous IL-6 and IL-10 levels were collected retrospectively. From these data, cytokine levels were compared between diagnoses with the Mann-Whitney U test. A logistic regression model was trained to classify PVRL versus uveitis from aqueous and vitreous IL-6 and IL-10 samples and compared with ISOLD scores and IL-10-to-IL-6 ratios. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC) for each classifier and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at the optimal cutoff (maximal Youden index) for each classifier. RESULTS: Seventy-seven lymphoma patients (10 aqueous samples, 67 vitreous samples) and 84 uveitis patients (19 aqueous samples, 65 vitreous samples) treated between October 5, 1999, and September 16, 2015, were included. Interleukin 6 levels were higher and IL-10 levels were lower in uveitis patients compared with lymphoma patients (P < 0.01). For vitreous samples, the logistic regression model, ISOLD score, and IL-10-to-IL-6 ratio achieved AUCs of 98.3%, 97.7%, and 96.3%, respectively. Sensitivity, specificity, PPV, and NPV at the optimal cutoffs for each classifier were 94.2%, 96.9%, 97%, and 94% for the logistic regression model; 92.7%, 100%, 100%, and 92.9% for the ISOLD score; and 94.2%, 95.3%, 95.6%, and 93.9% for the IL-10-to-IL-6 ratio. All models achieved complete separation between uveitis and lymphoma in the aqueous data set. CONCLUSIONS: The accuracy of the logistic regression model and generalizability of the ISOLD score to an independent patient cohort suggest that intraocular cytokine analysis by logistic regression may be a promising adjunct to cytopathologic analysis, the gold standard, for the early diagnosis of primary vitreoretinal lymphoma. Further validation studies are merited.

Post-intravitreal injection endophthalmitis secondary to Turicella otitidis: a case report.

BACKGROUND: Endophthalmitis is a rare but potentially devastating complication of intravitreal injection. The causative organism plays an important role in prognosis following endophthalmitis. Here we present the first reported case of Turicella otitidis endophthalmitis, which is notable for a delayed presentation. CASE PRESENTATION: A 71 year old male who was receiving intravitreal aflibercept injections for neovascular age-related macular degeneration presented 4 weeks after his most recent intravitreal injection and was found to have endophthalmitis. Polymerase chain reaction (PCR) testing of aqueous fluid was positive for Turicella otitidis. The endophthalmitis responded well to treatment with intravitreal antibiotics. CONCLUSIONS: Coryneform bacteria are a rare cause of endophthalmitis, and this is the first reported case of endophthalmitis caused by the corynebacterium species Turicella otitidis. As in this case, post-intravitreal injection endophthalmitis may have a bacterial etiology even with delayed presentation. The relatively indolent disease course and excellent response to intravitreal antibiotics is consistent with previous ophthalmic reports regarding other corynebacteria, as well as with otolaryngology and hematology oncology reports addressing Turicella otitidis specifically. This case supports the growing body of evidence for pathogenicity of Turicella otitidis and demonstrates the utility of PCR for diagnosis in small volume aqueous specimens.

Pharmacologic Treatment of Noninfectious Uveitis.

Uveitis encompasses a spectrum of diseases whose common feature is intraocular inflammation, which may be infectious or noninfectious in etiology (Nussenblatt and Whitcup 2010). Infectious causes of uveitis are typically treated with appropriate antimicrobial therapy and will not be discussed in this chapter. Noninfectious uveitides are thought have an autoimmune component to their etiology and are thus treated with anti-inflammatory agents.

Mutant ß-III spectrin causes mGluR1α mislocalization and functional deficits in a mouse model of spinocerebellar ataxia type 5.

Spinocerebellar ataxia type 5 (SCA5), a dominant neurodegenerative disease characterized by profound Purkinje cell loss, is caused by mutations in SPTBN2, a gene that encodes ß-III spectrin. SCA5 is the first neurodegenerative disorder reported to be caused by mutations in a cytoskeletal spectrin gene. We have developed a mouse model to understand the mechanistic basis for this disease and show that expression of mutant but not wild-type ß-III spectrin causes progressive motor deficits and cerebellar degeneration. We show that endogenous ß-III spectrin interacts with the metabotropic glutamate receptor 1α (mGluR1α) and that mice expressing mutant ß-III spectrin have cerebellar dysfunction with altered mGluR1α localization at Purkinje cell dendritic spines, decreased mGluR1-mediated responses, and deficient mGluR1-mediated long-term potentiation. These results indicate that mutant ß-III spectrin causes mislocalization and dysfunction of mGluR1α at dendritic spines and connects SCA5 with other disorders involving glutamatergic dysfunction and synaptic plasticity abnormalities.

Spectrin mutations cause spinocerebellar ataxia type 5.

We have discovered that beta-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families. Two families have separate in-frame deletions of 39 and 15 bp, and a third family has a mutation in the actin/ARP1 binding region. Beta-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane. We found marked differences in EAAT4 and GluRdelta2 by protein blot and cell fractionation in SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not mutant beta-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling.

Incident Ocular Inflammation After COVID-19 Infection in a US Veteran Population.

PURPOSE: To investigate whether COVID-19 infection is a risk factor for incident ocular inflammatory disease. DESIGN: Retrospective case-crossover study. METHODS: The US Veterans Health Administration Corporate Data Warehouse was used to identify patients with positive COVID-19 testing and incident ocular inflammatory disease between March 2020 and May 2022. The timing of incident ocular inflammation and COVID-19 testing was assessed for each participant to determine whether positive COVID-19 testing occurred 0-60 days prior to incident ocular inflammation diagnosis (risk period) or 15-75 days after incident ocular inflammation diagnosis (control period). The main outcome measure was the odds of positive COVID-19 testing in the risk period versus control period. RESULTS: Of the 1006 patients with incident ocular inflammation and a positive COVID-19 test in the study period, the age mean ± standard deviation was 62.6 ± 9.8 years and 840 (83%) were male. The odds of COVID-19 exposure was higher in the risk than control period (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.04-2.36; P = 0.03). Ocular inflammation was more likely to be bilateral in the risk period (OR, 3.97; 95% CI, 1.01-23.01; P = 0.03). Other ocular features and demographic characteristics were similar in the risk and control periods. Most cases of ocular inflammation were quiescent at the most recent eye examination. CONCLUSIONS: Incident ocular inflammation is associated with COVID-19 infection, but the increased risk is small, and the ocular inflammation is typically acute.

BILATERAL UVEITIS AND HYPOTONY FOLLOWING TREATMENT WITH TOPICAL CIDOFOVIR.

PURPOSE: To report a case of bilateral uveitis and hypotony associated with topical cidofovir treatment. METHODS: Case report. RESULTS: A 59-year-old diabetic man with HIV/AIDS presented with photophobia, ocular pain, and decreased vision. He was found to have bilateral hypotony, anterior uveitis, and serous choroidal detachments. Infectious disease workup, patient-reported history, and review of the patient's electronic medication list did not identify the etiology. Treatment with intensive topical corticosteroids led to resolution of uveitis and choroidal effusions within 3 months and resolution of hypotony within 9 months. Two years after his initial presentation, the patient developed acute recurrence of bilateral hypotony, anterior uveitis, and serous choroidal detachments shortly after intravenous cidofovir treatment. Careful reevaluation of the patient's outside medical records revealed that he had initiated treatment for rectal herpes simplex virus with compounded topical cidofovir one month before his initial presentation. CONCLUSION: To our knowledge, this is the first reported case of topical cidofovir causing ocular toxicity. Compounded and topical medications, like cidofovir in this case, may not appear on a patient's electronic medication list, so a focused review of outside medical records may be beneficial when a particular medication toxicity is suspected.

Glycated Hemoglobin Improvement After Medical and Surgical Eye Care in American Veterans Involves Multidisciplinary Care.

Purpose: The effects of diabetes mellitus (DM) on visual function have been extensively studied. Fewer studies evaluate the effect of visual function on DM, and previous small studies have shown mixed results concerning the relationship between glycated hemoglobin (HbA1c) and cataract surgery. We performed a retrospective, observational, single-site study at a Veterans hospital to evaluate this relationship and the relationship between HbA1c and non-surgical eye care. Patients and Methods: We compared pre- and post-operative/examination HbA1c in 431 surgical and 431 matched, non-surgical subjects who underwent eye examination at the same institution. Subgroup analysis was performed by age, elevated (≥8) pre-operative/examination HbA1c, and change in diabetic management. We also assessed for a relationship between changes in best-corrected visual acuity (BCVA) and HbA1c. The Minneapolis Veterans Affairs Health Care System Research Administration determined this study to be Institutional Review Board exempt from the requirements of 38 CFR 16 under Category 4 (iii). Results: Pairwise comparison of pre- versus post-operative HbA1c trended towards reduction at 3-6 months in all surgical subjects, with a statistically significant reduction in older subjects, and those with higher pre-operative HbA1c. Eye examination subjects experienced a significant HbA1c reduction 3-6 months after eye examination. Reduction in post-operative/examination HbA1c was associated with concurrent change in diabetic management. Conclusion: We found an overall reduction in HbA1c in diabetic Veterans who interacted with an ophthalmologist, whether for cataract surgery or eye examination. HbA1c reduction was greatest when ophthalmic care was delivered as part of a multidisciplinary care team. Our findings add new evidence to further support the importance of ophthalmic care in patients with DM and suggest improved visual function may facilitate improved glycemic control.

Therapeutic Outcomes of Non-Infectious Scleritis Treated with Tumor Necrosis Factor-Alpha Inhibitors.

PURPOSE: We determine the efficacy of tumor necrosis factor-α (TNF) inhibitors in establishing scleritis quiescence. METHODS: We conducted a multicenter retrospective chart review of patients with non-infectious scleritis treated with a TNF inhibitor for at least 6 months. The primary endpoint was scleritis quiescence at 6 months. Secondary endpoints included scleritis quiescence at 12 months, TNF inhibitor effects on concurrent doses of systemic corticosteroids and visual acuity outcomes at 6 and 12 months. RESULTS: At 6 months, 82.2% (37/45) of subjects obtained scleritis quiescence with TNF inhibition. At 12 months, 76.2% (32/42) of subjects remained quiescent. Baseline daily corticosteroid use (21.5 ± 21.6 mg) decreased to 5.4 ± 8.3 mg by 6 months (p < 0.0001) and 2.8 ± 6.1 mg by 12 months (p < 0.001). There was no significant difference between the baseline and 6-month BCVA (p = 0.52). CONCLUSIONS: TNF inhibitors are an effective scleritis therapy with significant systemic corticosteroid sparing effect.

Adverse COVID-19 outcomes in American Veterans with age-related macular degeneration: a case-control study.

OBJECTIVES: Prior studies suggest that patients with age-related macular degeneration (AMD) have poorer COVID-19 outcomes. This study aims to evaluate whether AMD is associated with adverse COVID-19 outcomes in a large clinical database. DESIGN: Case-control study. SETTING: We obtained demographic and clinical data from a national US Veterans Affairs (VA) database for all Veterans aged 50 years or older with positive COVID-19 testing prior to 2 May 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was hospitalisation. Secondary outcome measures were intensive care unit admission, mechanical ventilation and death. Potential associations between AMD and outcome measures occurring within 60 days of COVID-19 diagnosis were evaluated using multiple logistic regression analyses. RESULTS: Of the 171 325 patients in the study cohort, 7913 (5%) had AMD and 2152 (1%) had severe AMD, defined as advanced atrophic or exudative AMD disease coding. Multiple logistic regression adjusting for age, Charlson Comorbidity Index, sex, race, ethnicity and COVID-19 timing showed that an AMD diagnosis did not significantly increase the odds of hospitalisation (p=0.11). Using a Bonferroni-adjusted significance level of 0.006, AMD and severe AMD also were not significant predictors for the secondary outcomes, except for AMD being modestly protective for death (p=0.002). CONCLUSIONS: After adjusting for other variables, neither AMD nor severe AMD was a risk factor for adverse COVID-19 outcomes in the VA healthcare system. These findings indicate that an AMD diagnosis alone should not alter recommended ophthalmic management based on COVID-19 adverse outcome risk.

Characteristics and Outcomes of Patients with Scleritis in the IRIS® Registry (Intelligent Research in Sight) Database.

Purpose: To report patient characteristics and factors associated with poor visual acuity and abnormal intraocular pressure (IOP) in patients with scleritis in the American Academy of Ophthalmology's IRIS® Registry (Intelligent Research in Sight). Design: Retrospective cohort study. Participants: Patients in the IRIS Registry with at least 3 office visits associated with an International Classification of Diseases scleritis code from 2013 through 2019. Methods: We evaluated demographic and clinical characteristics in scleritis and scleritis subtype cohorts. We conducted Cox proportional hazards and multiple logistic regression analyses to assess associations with poor best-corrected visual acuity (BCVA), vision loss, and IOP abnormalities. Main Outcome Measures: Patient characteristics, BCVA of 0.6 logarithm of the minimum angle of resolution (logMAR) or more, BCVA worsened by more than 3 logMAR units 6 months after presentation, IOP of 30 mmHg or more, and IOP of 5 mmHg or less. Results: In this cohort of 111 314 patients with scleritis, the mean ± standard deviation age was 58.5 ± 16.6 years, 66% were women, and 30% had bilateral scleritis. Patients with scleromalacia perforans were older and more likely to have bilateral disease. Multiple logistic regression analysis identified factors with increased odds for poor presenting BCVA (older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes) and at least 3 lines of vision loss 6 months after initial scleritis diagnosis (older age, smoking, and anterior scleritis). Cox proportional hazards regression modeling of BCVA of 0.6 logMAR or more showed older age (adjusted hazard ratio [aHR] per 10-year unit, 1.11), Black race (aHR, 1.19), Hispanic ethnicity (aHR, 1.22), active smoking (aHR, 1.39), former smoking (aHR, 1.26), and certain scleritis subtypes increase the risk of poor visual acuity development (P < 0.001 for all). Older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes increased the odds of IOP abnormality. Conclusions: Older age, Black or Hispanic ancestry, smoking, and specific scleritis subtypes are risk factors for worse visual and IOP outcomes in patients with scleritis in the IRIS Registry. Closer follow-up may be appropriate for older, Black, or Hispanic patients with scleritis; smokers should receive smoking cessation assistance.

Survival in Patients with Neovascular Glaucoma Following Tube Shunt Implant or Cyclodestructive Procedure.

Purpose: The study purpose was to assess patient survival after tube shunt implant or cyclodestructive procedure for neovascular glaucoma and to determine whether specific preoperative factors are predictive of survival. Materials and methods: A retrospective chart review was performed on patients with neovascular glaucoma who underwent tube shunt implant and/or cyclodestructive procedure between January 2002 and December 2019 at the Minneapolis Veterans Affairs Health Care System. Patient survival was compared to the age and gender-matched Minnesota population. Cox regression analyses were performed to evaluate preoperative parameters and survival. Results: Tube shunt alone was implanted in 30 eyes, cyclodestruction alone was performed in nine eyes, and two eyes underwent both (n = 41 eyes, 39 patients). The postoperative 5-year survival rate was 62% in neovascular glaucoma patients compared to 80% in controls. Survival did not differ significantly based on neovascular glaucoma etiology. Preoperative best-corrected visual acuity of the neovascular glaucoma-affected eye (p = 0.05) and Charlson Comorbidity Index (p = 0.02) were associated with survival, but preoperative maximum intraocular pressure, hemoglobin A1c, and creatinine were not. The mean intraocular pressure at 6 months postprocedure was 14 mm Hg for tube shunt and 27 mm Hg for cyclodestruction (p = 0.03). Conclusion: Neovascular glaucoma patients have reduced survival, but the majority survived at least 5-year postprocedure. Ophthalmologists should consider patient survival and factors predictive of survival when planning procedures for neovascular glaucoma. Clinical significance: Our findings provide an updated perspective on survival in the setting of neovascular glaucoma and can help ophthalmologists provide patient-centered and holistic care. How to cite this article: Zhou Y, Coleman S, Boysen J, et al. Survival in Patients with Neovascular Glaucoma Following Tube Shunt Implant or Cyclodestructive Procedure. J Curr Glaucoma Pract 2022;16(2):74-78.

Rituximab for autoimmune retinopathy: Results of a Phase I/II clinical trial.

PURPOSE: This prospective study evaluates whether rituximab is a safe and potentially effective treatment for nonparaneoplastic autoimmune retinopathy (npAIR). MATERIALS AND METHODS: Five npAIR patients were enrolled in a Phase I/II, prospective, nonrandomized, open-label, single-center study. All patients received a cycle of 1000 mg intravenous rituximab at weeks 0 and 2, with a second cycle of rituximab 6 to 9 months later. Clinical evaluation was performed at baseline, 6 and 12 weeks after each rituximab cycle, and then every 3 months for a total duration of 18 months. The primary outcome for this study was treatment success based on visual field and full-field electroretinography at 6 months. The secondary outcomes included treatment success at months 12 and 18, drug-related adverse events, changes in visual symptoms, and changes in quality of life. RESULTS: Two patients met criteria for treatment success: one based solely on electroretinography and the other based solely on visual field area, but treatment success was not sustained. Clinical response over the course of the 18-month study showed disease stabilization in three patients and treatment failure in two patients. There were no severe drug-related adverse events. CONCLUSION: This is the first clinical trial prospectively evaluating the effect of rituximab in npAIR and, although rituximab was well tolerated, there was no clear-cut clinical improvement conferred by B cell depletion with rituximab.

Uveitis reactivation following recombinant zoster vaccination.

PURPOSE: Describe three cases of uveitis reactivation following immunization with recombinant zoster vaccine (RZV). OBSERVATIONS: One patient developed reactivation of previously controlled multifocal choroiditis within one week of receiving RZV, requiring treatment with systemic corticosteroids. Two patients with previously controlled anterior uveitis developed new anterior segment inflammation after RZV; both were treated with topical corticosteroids and systemic antiviral therapy. CONCLUSION AND IMPORTANCE: Uveitis recurrence is an infrequent but serious potential ocular side effect of recombinant zoster vaccination.

No association between cataract surgery and mitochondrial DNA damage with age-related macular degeneration in human donor eyes.

PURPOSE: To determine whether age-related macular degeneration (AMD) severity or the frequency of retinal pigment epithelium mitochondrial DNA lesions differ in human donor eyes that have undergone cataract surgery compared to phakic eyes. METHODS: Eyes from human donors aged ≥ 55 years were obtained from the Minnesota Lions Eye Bank. Cataract surgery status was obtained from history provided to Eye Bank personnel by family members at the time of tissue procurement. Donor eyes were graded for AMD severity using the Minnesota Grading System. Quantitative PCR was performed on DNA isolated from macular punches of retinal pigment epithelium to quantitate the frequency of mitochondrial DNA lesions in the donor tissue. Univariable and multivariable analyses were performed to evaluate for associations between (1) cataract surgery and AMD severity and (2) cataract surgery and mitochondrial DNA lesion frequency. RESULTS: A total of 157 subjects qualified for study inclusion. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that only age was associated with AMD grade. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that none of these factors were associated with retinal pigment epithelium mitochondrial DNA lesion frequency. CONCLUSIONS: In this study of human donor eyes, neither retinal pigment epithelium mitochondrial DNA damage nor the stage of AMD severity are independently associated with cataract surgery after adjusting for other AMD risk factors. These new pathologic and molecular findings provide evidence against a relationship between cataract surgery and AMD progression and support the idea that cataract surgery is safe in the setting of AMD.

Cancer-Associated Retinopathy due to Clear Cell Renal Carcinoma.

An 84-year-old female presented with bilateral scotomas and progressive nyctalopia over 1 year. Best-corrected visual acuity was 20/50 in both eyes with reduced color vision. Goldmann visual field showed bilateral cecocentral scotomas and generalized constriction of the visual fields. This led to an electroretinogram showing an electronegative pattern consistent with autoimmune retinopathies. Infectious workup was negative. Anti-retinal antibodies were positive, leading to a presumed diagnosis of cancer-associated retinopathy (CAR). Imaging showed a previously unknown left renal lower pole mass, and she underwent a radical nephrectomy. Biopsy showed nuclear grade-3 clear cell renal carcinoma staged T1. The patient was treated with oral prednisone with no ocular improvement. We report on a rare case of clear cell renal carcinoma causing CAR. CAR is an important paraneoplastic syndrome to diagnose since the majority of ocular cases precede other manifestations of malignancy. Therefore, a timely diagnosis of CAR can be lifesaving or at least life-extending.

Thrombocytopenia and clear corneal incision cataract surgery.

PURPOSE: To investigate complications and outcomes of clear corneal incision cataract surgery in patients with thrombocytopenia. SETTING: 1 veterans hospital and 2 academic medical centers. DESIGN: Multicenter retrospective chart review. METHODS: All eyes of thrombocytopenic patients that underwent clear corneal incision cataract surgery with a platelet count of 100 × 103/µL or less measured within 30 days prior to surgery were included. Subject demographics, intraoperative complications, use of pupillary expansion devices, use of local anesthetic injections, and change in corrected distance visual acuity were recorded. RESULTS: 3 sites recorded 40 113 clear corneal incision cataract surgeries, of which 196 eyes (0.49%) of 150 thrombocytopenic patients were recorded. The mean platelet count in the study subjects was 73.0 ± 20.5 × 103/µL. Two cases of intraoperative iris hemorrhage that were readily and controlled occurred in conjunction with pupillary expansion. There were no bleeding complications associated with retrobulbar, peribulbar, or sub-Tenon anesthetic injections. There was a statistically significant improvement (P < .0001) in visual acuity post-operatively. CONCLUSIONS: Clear corneal incision cataract surgery with pupillary expansion devices and local anesthetic injections can be safely performed in patients with thrombocytopenia.