Importance of Baseline Fluorescein Angiography for Patients Presenting to Tertiary Uveitis Clinic.

PURPOSE: To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic. DESIGN: Retrospective comparison of diagnostic approaches. METHODS: Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by three uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc, Dunfermline, Scotland, UK), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering, Heidelberg, Germany) and UWFFA (Optos Plc, Dunfermline, Scotland, UK) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA, compared with Set 1. RESULTS: The mean age of the patients was 46.9±22.4 (range, 7-96) and 91 (57.6%) were female. With Set 1 alone, 138 (55.2%) eyes were found to have active disease; localization was anterior in 58 (42.0%) eyes, posterior in 53 (38.4%) eyes and anterior + posterior in 27 (19.6%) eyes. With Set 2, 169 eyes of 107 patients had active anterior, posterior or pan-uveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 (18.3%) eyes with active disease (p=0.006), and additional 31 (18.3%) eyes having disease in both anterior + posterior segments (p<0.001). Regarding the primary outcome, management was changed in 68 (27.4%) eyes in Set 2, compared to Set 1. CONCLUSION: Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared to clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of uveitis patients at the baseline visit.

Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies.

BACKGROUND: Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period. MAIN FINDINGS: We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL). SHORT CONCLUSION: CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

The Role of Corticosteroids and Immunomodulatory Therapy in the Management of Infectious Uveitis.

PURPOSE: The index review aims to provide an update on the role of corticosteroids and steroid-sparing immunomodulatory therapy (IMT) in managing patients with infectious uveitis. METHOD: Narrative literature review. RESULTS: Corticosteroids and immunomodulatory therapy (IMT) focus on the host defense system instead of the pathogen, adjusting exaggerated inflammatory reactions to reduce potential harm to ocular tissues. Systemic or local corticosteroids are primarily selected as adjunctive medication for infectious uveitis. Concomitant corticosteroids have also been used in cases of paradoxical worsening in ocular tuberculosis and immune recovery uveitis in cytomegalovirus (CMV) retinitis. While there is no well-established evidence to support the use of IMT in infectious uveitis, it is occasionally used in clinical settings to treat persistent inflammation following resolution of infection such as cases of ocular tuberculosis and ocular syphilis where an insufficient response is observed with corticosteroids. CONCLUSION: There is no consensus on the position of immunomodulatory therapy in the management of infectious uveitis with different etiologies. The index review provides an overview of available adjunctive corticosteroids and IMT options to assist clinicians in managing such disease entities more efficiently.

Ocular manifestations and clinical outcomes in Tubulointerstitial Nephritis and Uveitis Syndrome (TINU).

PURPOSE: To describe the various ocular clinical features and visual outcomes in Tubulointerstitial Nephritis and Uveitis Syndrome (TINU). METHODS: The medical records of 13 patients (26 eyes) diagnosed with TINU were reviewed. RESULTS: Twenty-six (26) eyes of 13 patients with TINU were reviewed in this study. The median age at onset of uveitis was 14 (range, 9-45). Eight (61.5%) subjects were female. The median follow-up of patients was 30 months (range, 6-89 months). Posterior segment findings were seen in 18 eyes of 9 patients (69.2%). The most common posterior findings were optic nerve head inflammation (16 eyes, 88.8%) and retinal vasculitis (13 eyes, 72.2%). Other posterior findings included vitritis (8 eyes, 44.4%), macular edema (6 eyes, 33.3%), snowball (4 eyes, 22.2%), and chorioretinal lesions (2 eye, 11.1%). Eight patients had fluorescein angiography (FA) data available and most eyes had retinal capillary leakage (13 eyes, 81.2%) followed by optic disc staining/leakage (12 eyes, 75%). Twelve (12) patients (92.3%) were treated with immunomodulatory treatment (IMT) and/or biologics. Five patients (%38.4) required biologics to control intraocular inflammation. CONCLUSION: Posterior segment involvement may be common in patients with TINU syndrome. FA provides significant information for detecting posterior segment involvement and disease activity in TINU. The majority of patients required systemic treatment in order to control intraocular inflammation and prevent relapses.

Recent advances in uveitis therapy: focus on selected phase 2 and 3 clinical trials.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.

Birdshot Chorioretinopathy in Early Adulthood: Review of Current Literature and Case Report.

Purpose: We describe the course of a patient diagnosed with birdshot chorioretinopathy (BSCR) in early adulthood and summarize clinical findings from similar BSCR patients reported in the literature. Observations: A 37-year-old male presented to our tertiary uveitis facility with bilateral ocular discomfort, hazy vision, and floaters. Ocular examination was notable for vitritis, optic disc edema, and ovoid hypopigmented chorioretinal lesions, visible on indocyanine green chorioangiography as multiple hypocyanescent spots in the intermediate phase. Full-field electroretinography and visual evoked potential showed global retinal dysfunction and optic nerve dysfunction. Laboratory evaluations were notable only for human leukocyte antigen (HLA)-A29 positivity. The patient was diagnosed with BSCR and started on oral prednisone and eventually managed with infliximab. Conclusions and Importance: BSCR can affect patients in early adulthood. Proper diagnostic work-up, including assessing HLA-A29 positivity, is needed to manage atypical cases.

Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

Pars plana vitrectomy with internal limiting membrane flap versus pars plana vitrectomy with conventional internal limiting membrane peeling for large macular hole.

BACKGROUND: Macular hole (MH) is a full-thickness defect in the central portion of the retina that causes loss of central vision. According to the usual definition, a large MH has a diameter greater than 400 µm at the narrowest point. For closure of MH, there is evidence that pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling achieves better anatomical outcomes than standard PPV. PPV with ILM peeling is currently the standard of care for MH management; however, the failure rate of this technique is higher for large MHs than for smaller MHs. Some studies have shown that the inverted ILM flap technique is superior to conventional ILM peeling for the management of large MHs. OBJECTIVES: To evaluate the clinical effectiveness and safety of pars plana vitrectomy with the inverted internal limiting membrane flap technique versus pars plana vitrectomy with conventional internal limiting membrane peeling for treating large macular holes, including idiopathic, traumatic, and myopic macular holes. SEARCH METHODS: The Cochrane Eyes and Vision Information Specialist searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries on 12 December 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated PPV with ILM peeling versus PPV with inverted ILM flap for treatment of large MHs (with a basal diameter greater than 400 µm at the narrowest point measured by optical coherence tomography) of any type (idiopathic, traumatic, or myopic). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and assessed the certainty of the body of evidence using GRADE. MAIN RESULTS: We included four RCTs (285 eyes of 275 participants; range per study 24 to 91 eyes). Most participants were women (63%), and of older age (range of means 59.4 to 66 years). Three RCTs were single-center trials, and the same surgeon performed all surgeries in two RCTs (the third single-center RCT did not report the number of surgeons). One RCT was a multicenter trial (three sites), and four surgeons performed all surgeries. Two RCTs took place in India, one in Poland, and one in Mexico. Maximum follow-up ranged from three months (2 RCTs) to 12 months (1 RCT). No RCTs reported conflicts of interest or disclosed financial support. All four RCTs enrolled people with large idiopathic MHs and compared conventional PPV with ILM peeling versus PPV with inverted ILM flap techniques. Variations in technique across the four RCTs were minimal. There was some heterogeneity in interventions: in two RCTs, all participants underwent combined cataract-PPV surgery, whereas in one RCT, some participants underwent cataract surgery after PPV (the fourth RCT did not mention cataract surgery). The critical outcomes for this review were mean best-corrected visual acuity (BCVA) and MH closure rates. All four RCTs provided data for meta-analyses of both critical outcomes. We assessed the risk of bias for both outcomes using the Cochrane risk of bias tool (RoB 2); there were some concerns for risk of bias associated with lack of masking of outcome assessors and selective reporting of outcomes in all RCTs. All RCTs reported postoperative BCVA values; only one RCT reported the change in BCVA from baseline. Based on evidence from the four RCTs, it is unclear if the inverted ILM flap technique compared with ILM peeling reduces (improves) postoperative BCVA measured on a logarithm of the minimum angle of resolution (logMAR) chart at one month (mean difference [MD] -0.08 logMAR, 95% confidence interval [CI] -0.20 to 0.05; P = 0.23, I2 = 65%; 4 studies, 254 eyes; very low-certainty evidence), but it may improve BCVA at three months or more (MD -0.17 logMAR, 95% CI -0.23 to -0.10; P < 0.001, I2 = 0%; 4 studies, 276 eyes; low-certainty evidence). PPV with an inverted ILM flap compared to PPV with ILM peeling probably increases the proportion of eyes achieving MH closure (risk ratio [RR] 1.10, 95% CI 1.02 to 1.18; P = 0.01, I2 = 0%; 4 studies, 276 eyes; moderate-certainty evidence) and type 1 MH closure (RR 1.31, 95% CI 1.03 to 1.66; P = 0.03, I² = 69%; 4 studies, 276 eyes; moderate-certainty evidence). One study reported that none of the 38 participants experienced postoperative retinal detachment. AUTHORS' CONCLUSIONS: We found low-certainty evidence from four small RCTs that PPV with the inverted ILM flap technique is superior to PPV with ILM peeling with respect to BCVA gains at three or more months after surgery. We also found moderate-certainty evidence that the inverted ILM flap technique achieves more overall and type 1 MH closures. There is a need for high-quality multicenter RCTs to ascertain whether the inverted ILM flap technique is superior to ILM peeling with regard to anatomical and functional outcomes. Investigators should use the standard logMAR charts when measuring BCVA to facilitate comparison across trials.

ASSOCIATION OF ORAL MONTELUKAST WITH REDUCED ODDS OF DEVELOPING EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development. METHODS: This case-control study was conducted using institutional cohort finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Subanalysis among 1913 exAMD and 324 nonexudative AMD was also conducted. RESULTS: A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use before exAMD diagnosis, compared with 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted odds ratio [OR]: 0.50, 95% confidence interval: 0.31-0.80) and nonsteroidal anti-inflammatory drug usage (adjusted OR: 0.69). Caucasian race, history of smoking, and nonexudative macular degeneration in either eye were also found to have a significant relationship with increased odds of exAMD. In the subanalysis, montelukast usage showed significant association with reduced odds of developing exAMD from nonexudative AMD (adjusted OR: 0.53, 95% confidence interval: 0.29-0.97) and the presence of atopic disease (adjusted OR: 0.60). CONCLUSION: The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

Posterior Segment Ocular Findings in HLA-B27 Positive Patients with Uveitis: A Retrospective Analysis.

Purpose: To describe the prevalence and characteristics of posterior segment manifestations in patients with HLA-B27-associated uveitis using wide field imaging. Methods: Medical records of patients diagnosed with HLA-B27-associated uveitis from a tertiary uveitis clinic were reviewed. Posterior segment involvements including but not limited to peripheral vasculitis, optic disc inflammation, and macula edema documented based on medical records and various imaging modalities including wide field fluorescein angiography and optical coherence tomography, were noted. Demographic characteristics, accompanied with systemic diseases as well as duration and chronicity of uveitis, were also evaluated. Patients with significant systemic and ocular comorbidities were excluded. Statistical analyses including chi-squared tests and paired t-tests were employed. Results: Of the 44 patients with HLA-B27 associated uveitis, 22 patients (50%) were noted to demonstrate posterior segment involvement. Disc leakage and peripheral vasculitis were the most common findings of posterior involvement. Those with anterior chamber inflammation were found to have a significantly increased risk of posterior involvement. Those with posterior involvement were also noted to have a statistically significant decreased visual acuity. No significant association was found between documented duration of disease and posterior segment involvement. Conclusion: The prevalence of posterior segment involvement in HLA-B27 associated uveitis is higher compared to previous reports when evaluated with wide angle imaging modalities. Careful examination of the posterior segment is required in patients with HLA-B27 associated uveitis.

Evaluation of correlation between Diopsys® NOVA™ fixed-luminance flicker ERG and Diagnosys® Espion 2™ flicker ERG parameters.

PURPOSE: Diopsys® NOVA™ is a novel full-field electroretinography (ffERG) device that can make rapid measurements of retinal electrophysiologic function. Diagnosys® Espion 2™ is a clinical gold-standard ERG device. This study aimed to investigate whether light-adapted Diopsys® NOVA™ fixed-luminance flicker ffERG magnitude and implicit time (converted from phase) measurements correlate with light-adapted Diagnosys® Espion 2™ flicker ffERG amplitude and implicit time measurements, respectively. METHODS: Twelve patients (22 eyes) with various retinal and uveitic diseases underwent light-adapted Diagnosys® Espion 2™ and Diopsys® NOVA™ fixed-luminance flicker testing. Diopsys® magnitude and implicit time (converted from phase) measurements were compared to Diagnosys® amplitude and implicit time measurements, and a Pearson correlation was used to evaluate any existing correlation. Groups were also compared using generalized estimating equations. Bland-Altman plots were utilized to determine agreement between the comparison groups. RESULTS: Age of patients ranged from 14 to 87 years. 58% (n = 7/12) of patients were female. A significant, positive correlation (r = 0.880, P < 0.001) was observed between magnitude (Diopsys®) and amplitude (Diagnosys®) measurements. Amplitude increases by 6.69 µV for each 1 µV increase in Magnitude (p-value < 0.001). A statistically significant, strong positive correlation was observed between Diopsys® implicit time measurements (converted from phase) and Diagnosys® implicit time measurements (r = 0.814, p-value < 0.001). For each 1 ms increase in Diopsys® implicit time, Diagnosys® implicit time increases by 1.13 ms (p-value < 0.001). CONCLUSIONS: There is a statistically significant positive correlation between light-adapted Diopsys® NOVA™ fixed-luminance flicker amplitude and Diagnosys® flicker magnitude values. Additionally, there is a statistically significant positive correlation between Diopsys® NOVA™ fixed-luminance flicker implicit time (converted from phase) and Diagnosys® flicker implicit time values. These results imply that the Diopsys® NOVA™ module, which utilizes the nonstandard shortened International Society for Clinical Electrophysiology of Vision (ISCEV) ERG protocol, can produce reliable light-adapted flicker ffERG measurements.

Birdshot chorioretinopathy in an HLA-A29 positive Asian patient.

Purpose: To present a case of birdshot chorioretinopathy (BCR) in a Chinese patient with HLA-A29 positivity. Observations: A 45-year-old Chinese female presented at a tertiary Ophthalmology Clinic with complaints of frequent headaches as well as blurred vision, photophobia, and pressure in the left eye (OS). The patient had a significant ocular history of left orbital cavernous hemangioma status post lateral orbitotomy and resection. Uncorrected visual acuity was 20/20 in the right eye (OD) and 20/40 in OS (pinhole 20/30). Funduscopic examination demonstrated optic disc edema, left eye worse than right eye, and vascular tortuosity in both eyes (OU). Late phase fluorescein angiography (FA) showed extensive perivascular and optic disc leakage and peripheral capillary leakage in OU. Laboratory evaluations were positive for human leukocyte antigen-A29 (HLA-A29). The patient was started on 40 mg prednisone daily; mycophenolate mofetil 500 mg twice daily was subsequently added.At the 3-month consultation visit to the Uveitis Clinic, dilated funduscopic examination revealed 1+ vitreous cells and improved optic disc edema in OU. FA showed improved vascular and optic disc leakage in OS but worsened leakage in OD. At this point, indocyanine green angiography (ICGA) was ordered which revealed hypocyanescent lesions throughout the choroid that were centered on the optic disc, supporting and confirming the diagnosis of BCR. Conclusions and Importance: The index patient is the first reported case of BCR in an HLA-A29 positive Asian patient.

Cataract surgery in patients with retinitis pigmentosa: systematic review.

Retinitis pigmentosa (RP) is an inherited bilateral retinal degenerative disease with an incidence of 1 in 4000 people. RP affects more than 1 million individuals worldwide. Although night blindness and restricted visual field are the most typical symptoms of these individuals, generalized vision loss due to cataracts can be expected in the latter stages of the disease. It has been demonstrated that posterior subcapsular cataract is the most prevalent cataract in younger individuals with RP, as opposed to age-related cataracts. Although most ophthalmologists may have a negative view of cataract surgery in patients with RP, it appears that it can play an important role in the visual restoration of patients with RP. However, there are concerns about performing cataract surgery for patients with RP. Herein, a systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses on databases of MEDLINE and Scopus.

Acute idiopathic blind spot enlargement syndrome (AIBSES) with retinal vasculitis.

Purpose: To report the clinical and anatomical features of an unusual case of acute idiopathic blind spot enlargement syndrome (AIBSES) with retinal vasculitis. Observations: A 39-year-old patient, who was a known case of chronic headache with nonspecific visual symptoms for nine years, developed scotomas in her right eye. She was initially diagnosed with AIBSES which had been stable, but later worsened with symptoms of subsequent blind spot enlargement and photopsia on the left eye a year later. Increase in the size of the blind spot over the left eye and stability of the blind spot enlargement over the right eye was documented on Humphrey visual field (HVF) testing. Due to the rapid onset and severity of symptoms, an inflammatory etiology was entertained and this prompted referral to our clinic. At initial presentation, fluorescein angiogram (FA) revealed moderate diffuse vasculitis and disc leakage in the left eye, which existed alongside the enlarged blind spot. Corticosteroid treatment was suggested and initiated. The patient was found to have a reduction in the size of her blind spot and a decrease in severity of retinal vasculitis a month later. Unfortunately, the patient was then lost to follow up and had stopped steroid treatment of her own accord. After nine months without treatment, the patient's blind spot increased to a larger size than her initial presentation, as documented on HVF, with recurrence of vasculitis in the left eye. Conclusion and Importance: This is an unusual case of AIBSES which presented with vasculitis and rapid progression and has responded to steroids. Though monocular AIBSES has been shown to later affect the contralateral eye, concurrent vasculitis with AIBSES has not previously been reported. Furthermore, the response to treatment with reduction in blind spot enlargement is unusual for AIBSES. These findings stress the need for regular monitoring in cases of AIBSES.

Electroretinographic findings in retinal vasculitis.

AIM: To describe and correlate electroretinographic responses with clinical and angiographic findings in retinal vasculitis (RV). METHODS: Medical records of patients with diagnosis of RV at a tertiary eye centre from December 2017 to May 2021 were reviewed. Cases in which fluorescein angiography (FFA) and full field electroretinography (ffERG) were done within 1 month were included. FFAs were graded according to the Angiography Scoring for Uveitis Working Group from 0 to 40, where 0 is normal. A novel ffERG grading system was implemented where individual waves were graded for timing and amplitude and general ffERG score was determined with 6 being a perfect score. RESULTS: 20 patients (34 eyes) were included. Mean age was 43.9±19.8 years; 70% were female. Median best-corrected visual acuity was 0.8 (0.08-1). Mean FFA score was 12.6±6.5. Median general ffERG score was 5 (0-6). 68% and 91% of eyes had responses with general ffERG scores ≥5 and 4, respectively. Flicker timing was most commonly affected.FFA scores weakly correlated with delayed photopic cone b-wave and flicker timing (p=0.03 and 0.016, respectively). Vitreous haze moderately correlated with delayed cone b-wave timing (p<0.001), delayed flicker timing (p=0.002) and weakly correlated with lower flicker amplitude (p=0.03). Underlying systemic disease was associated with poor ffERG responses. CONCLUSION: In this study, RV was not frequently associated with severe global retinal dysfunction Higher FFA scores, and vitreous haze grading were weakly, but significantly, correlated with cone-generated ffERG responses.

Longitudinal Comparative Analysis of Semi-Automated Aqueous Flare Measurements with Clinical Grading and Visual Outcomes in Uveitic Eyes.

PURPOSE: To evaluate the correlation between longitudinal changes in aqueous flare measured by laser flare photometer (LFP), best-corrected visual acuity (BCVA), and clinical grade using both Standardization of Uveitis Nomenclature (SUN) and modified SUN (MSUN) scales uveitis patients. METHODS: Patients were classified according to both SUN and MSUN grading scales. LFP measurements were acquired (Kowa FM-700) at each visit. Mean change in LFP was assessed longitudinally, comparing with those in visual acuity, SUN, and MSUN grading scales. RESULTS: Mean change in LFP was correlated to those in BCVA (p = .018), SUN scale (p < .001), and MSUN scale (p = .008). Cases within same initial SUN (0 and 1+) and MSUN (0.5+ and 1+) grades and different longitudinal flare prognosis (decreased/unchanged/increased) had significantly different initial LFP values (all p < .05). CONCLUSIONS: LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP.

Neurosarcoidosis, Coccidioidomycosis, or Both!

Purpose: To report a case of neurosarcoidosis (NS) who was initially diagnosed as Coccidioidomycosis immitis (CI) infection. Observations: A 57-year-old diabetic man presented with sudden painless diminution of vision, metamorphopsia, and color vision deficits in the left eye (OS) for one month. His vision was 20/20 in the right eye (OD) and 20/40 OS. Ophthalmic examination revealed left relative afferent pupillary defect, blurred optic nerve margin, creamy chorioretinal infiltration around the optic disc, and mild macular edema. OD examination was non-revealing. Chest CT scan with contrast showed calcified mediastinal lymph nodes, but biopsy of the lymph nodes was normal. Brain and orbit MRI demonstrated soft tissue abnormality with enhancement in left orbital apex with involvement of the extraocular muscles. CSF culture was negative, but complement fixation had positive titer of 1:2 for CI. The patient was diagnosed with CI meningitis, and antifungal therapy was initiated. Slight visual and symptomatic improvement was observed, which was not completely satisfactory. Biopsy of extraocular orbital muscle five months later revealed non-caseating granulomatous inflammation, leading to initiation of prednisone trial therapy. Nine months later, the patient was referred to a tertiary center owing to persistence of optic disc edema OS. PET CT was consistent with a diagnosis of sarcoidosis. Antifungal treatment was discontinued, and oral prednisone with methotrexate was initiated. Subsequently, methotrexate was replaced by infliximab to further manage ocular inflammation and neurologic symptoms which was effective. Vision was 20/20 OD and 20/30 OS at the most recent visit. Conclusion and Importance: Signs and symptoms of neurosarcoidosis and coccidioidomycosis can be similar and deceiving. The index case underscores importance of considering appropriate differential diagnoses in patients with similar symptoms and signs who may respond to preliminary designated treatment but not to the optimal extent. Considering such possibility could assist clinicians in managing the patients timely and efficiently.

Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies.

PURPOSE: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies. METHODS: Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score. RESULTS: Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 µm to 298.2 ± 40.3 µm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases. CONCLUSION: IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

Multifocal electroretinographic findings in angiographic macular leakage in the setting of intermediate, posterior, or panuveitis.

OBJECTIVE: To evaluate the functional implications of angiographic macular leakage without the presence of intraretinal fluid on optical coherence tomography (OCT) in eyes with intermediate, posterior, or panuveitis. METHODS: Retrospective study on patients with a diagnosis of intermediate, posterior, or panuveitis. Patients who had fluorescein angiography, OCT, and multifocal electroretinography (mfERG) within a predetermined time frame were included. Demographic and clinical data including types of ocular inflammation and best-corrected visual acuity (BCVA), in addition to OCT, fluorescein angiography, and mfERG data were collected. The study cohort was divided into 2 groups based on the presence of angiographic macular leakage and macular edema (ME): group 1 (no ME and no macular leakage) and group 2 (presence of macular leakage without ME). RESULTS: A total of 29 patients (43 eyes) were included in the study, with 13 patients (17 eyes) in group 1 and 16 patients (26 eyes) in group 2. No statistically significant differences in age, sex, anterior-chamber cells, lens status, vitreous cells, vitreous haze, BCVA, or mean central subfoveal thickness were found between groups 1 and 2. All mfERG values, including N1 and P1 response densities and timings for rings 1-5, did not show any statistically significant difference between group 1 and 2. No correlation was found between either BCVA or central subfoveal thickness and any of mfERG values for rings 1-3. CONCLUSIONS: In absence of ME, angiographic macular leakage in eyes with uveitis might not be associated with worse macular function when compared with eyes without angiographic macular leakage.