Mimickers of anterior uveitis, scleritis and misdiagnoses- tips and tricks for the cornea specialist.

BACKGROUND: Anterior uveitis, inflammation of the anterior chamber and related structures, is a cohort of diseases that can present to almost any general or sub-specialty Ophthalmology practice. Its features classically involve anterior chamber cell and flare. Below the surface of these two signs exist a panoply of diagnoses. BODY: The purpose of this review is to provide a general framework for diagnoses of anterior uveitis that are often missed as well as non-uveitic pathologies that often mimic anterior uveitis. Diagnostic deviation in either direction can have vision-threatening and rarely life-threatening consequences for patients. Using a comprehensive literature review we have collected a broad spectrum of etiologies of anterior uveitis that are easily missed and non-uveitic pathologies that can masquerade as anterior uveitis. CONCLUSIONS: We present a focused review on specific misdiagnosed anterior uveitis pathologies and some of the conditions that can masquerade as anterior uveitis and scleritis.

Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Multimodal Imaging Based Predictors for the Development of Choroidal Neovascularization in Patients with Central Serous Chorioretinopathy.

This study evaluated predictors for choroidal neovascularization (CNV) associated with central serous chorioretinopathy (CSCR) based on multimodal imaging. A retrospective multicenter chart review was conducted on 134 eyes of 132 consecutive patients with CSCR. Eyes were classified as per the multimodal imaging-based classification of CSCR at baseline into simple/complex CSCR and primary episode/recurrent/resolved CSCR. Baseline characteristics of CNV and predictors were evaluated with ANOVA. In 134 eyes with CSCR, 32.8% had CNV (n = 44) with 72.7% having complex CSCR (n = 32), 22.7% having simple (n = 10) and 4.5% having atypical (n = 2). Primary CSCR with CNV were older (58 vs. 47, p = 0.00003), with worse visual acuity (0.56 vs. 0.75, p = 0.01) and of longer duration (median 7 vs. 1, p = 0.0002) than those without CNV. Similarly, recurrent CSCR with CNV were older (61 vs. 52, p = 0.004) than those without CNV. Patients with complex CSCR were 2.72 times more likely to have CNV than patients with simple CSCR. In conclusion, CNV associated with CSCR was more likely in complex CSCR and older age of presentation. Both primary and recurrent CSCR are implicated in CNV development. Patients with complex CSCR were 2.72 times more likely to have CNV than patients with simple CSCR. Multimodal imaging-based classification of CSCR supports detailed analysis of associated CNV.

Ocular symptoms in COVID-19 infection: a survey study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) systemic symptoms and sequelae have been studied extensively, but less is known about the characterization, duration, and long-term sequelae of ocular symptoms associated with COVID-19 infection. The purpose of this study was to analyze the frequency, spectrum, and duration of ocular symptoms in participants with COVID-19 infection treated in inpatient and outpatient settings. METHODS: A retrospective electronic survey was distributed to NIH employees and the public who reported testing positive for SARS-CoV-2. The anonymous survey collected information on demographics, past ocular history, systemic COVID-19 symptoms, and ocular symptoms. RESULTS: A total of 229 (21.9% male and 78.1% female, mean age 42.5 ± 13.9) survey responses were included. Ocular symptoms were reported by 165 participants with a mean of 2.31 ± 2.42 symptoms. The most commonly reported ocular symptoms were light sensitivity (31.0%), itchy eyes (24.9%), tearing (24.9%), eye redness (24.5%), and eye pain (24.5%). Participants with ocular symptoms had a higher number of systemic symptoms compared to participants without ocular symptoms (mean 9.17 ± 4.19 vs 6.22 ± 3.63; OR: 1.21; 95% CI: 1.11 - 1.32; p < 0.001). Ocular symptoms were more common in those who reported a past ocular history compared to those who did not (81.8% vs 67.1%; OR: 2.17; 95% CI: 1.08 - 4.37; p = 0.03). Additionally, the onset of ocular symptoms occurred most frequently at the same time as systemic symptoms (47.5%), and 21.8% reported symptoms lasting ≥ 14 days. CONCLUSIONS: Ocular surface-related symptoms are the most frequent ocular manifestations, and systemic disease severity is associated with the presence of ocular symptoms. Additionally, our results show that ocular symptoms can persist post-COVID-19 infection. Further work is needed to better understand ocular symptoms in COVID-19 and long-term sequelae.

Ocular Symptoms In COVID-19 Infection: A Survey Study.

Background: Coronavirus disease 2019 (COVID-19) systemic symptoms and sequelae have been studied extensively, but less is known about the characterization, duration, and long-term sequelae of ocular symptoms associated with COVID-19 infection. The purpose of this study was to analyze the frequency, spectrum, and duration of ocular symptoms in participants with COVID-19 infection treated in inpatient and outpatient settings. Methods: A retrospective electronic survey was distributed to NIH employees and the public who reported testing positive for SARS-CoV-2. The anonymous survey collected information on demographics, past ocular history, systemic COVID-19 symptoms, and ocular symptoms. Results: A total of 229 (21.9% male and 78.1% female, mean age 42.5 ±13.9) survey responses were included. Ocular symptoms were reported by 165 participants with a mean of 2.31±2.42 symptoms. The most commonly reported ocular symptoms were light sensitivity (31.0%), itchy eyes (24.9%), tearing (24.9%), eye redness (24.5%), and eye pain (24.5%). Participants with ocular symptoms had a higher number of systemic symptoms compared to participants without ocular symptoms (mean 9.17 ± 4.19 vs 6.22 ± 3.63; OR: 1.21; 95% CI: 1.11 - 1.32; p<0.001). Ocular symptoms were more common in those who reported a past ocular history compared to those who did not (81.8% vs 67.1%; OR: 2.17; 95% CI: 1.08 - 4.37; p=0.03). Additionally, the onset of ocular symptoms occurred most frequently at the same time as systemic symptoms (47.5%), and 12.6% reported symptoms lasting ≥14 days. Conclusions: Ocular surface-related symptoms are the most frequent ocular manifestations, and systemic disease severity is associated with the presence of ocular symptoms. Additionally, our results show that ocular symptoms can persist post-COVID-19 infection. Further work is needed to better understand ocular symptoms in COVID-19 and long-term sequelae.

The Association between QuantiFERON-TB Gold Test and Clinical Manifestations of Uveitis in the United States.

PURPOSE: To report the prevalence of QuantiFERON-TB Gold (QFT-G) positivity among uveitis patients compared to general population and to evaluate the differences in clinical features of uveitis. DESIGN: Retrospective cohort study. METHODS: SETTING: Institutional. PATIENT POPULATION: 418 consecutive new uveitis patients, regardless of clinical suspicion, were tested for QFT-G. OBSERVATION PROCEDURES: Demographics, TB risk factors, clinical characteristics of uveitis were collected. MAIN OUTCOME MEASURES: The frequency of QFT-G positivity among uveitis patients and characteristic clinical features among QFT-G positive patients. RESULTS: QFT-G positivity was found in 60/418 patients with uveitis (14.4%, 95% CI: 11.18 - 18.14) higher than the general US population (5%, 95% CI: 4.2 - 5.8, p<.001). Age, gender and residence were similar between QFT-G positive and negative groups. Uveitis patients with positive QFT-G were more likely to be foreign born or have a recent travel history (OR:5.84; 95% CI: 2.83 - 12.05; p<.001). QFT-G positive patients were more likely to present with granulomatous uveitis (OR 2.90; 95%CI 1.36 - 6.21; p=.006). No significant association was found with specific clinical features such as choroiditis, retinal vasculitis, occlusive vasculitis, and serpiginoid choroiditis (p>.05 for each). Prevalence of TB-uveitis based on treatment response was 1.19%. CONCLUSIONS: Our study demonstrates significantly higher prevalence of QFT-G positivity among uveitis patients compared to average US population. Characteristic signs of TB uveitis reported in endemic countries were not seen in this cohort. Implications of higher prevalence of QFT-G positivity among uveitis patients require further investigation.

Optical Coherence Tomography Angiography Changes in Choroidal Vasculature following Treatment in Punctate Inner Choroidopathy.

Purpose: To describe the changes seen on optical coherence tomography angiography [OCTA] in patients with PIC following immunosuppressive therapy.Methods: We reviewed serial OCTA scans from five consecutive PIC patients (5 eyes) with at least 3 months of follow-up, who underwent imaging before and after immunosuppressive therapy. Using ImageJ, superficial and deep retinal vasculature were analyzed for vessel area and foveal avascular zone. Choriocapillaris layer was analyzed for flow signal loss.Results: Five out of five patients received an orbital floor triamcinolone acetonide injection as the initial treatment for periods of activity. Mean choriocapillaris (CC) flow void area obtained after immunosuppressive therapy was significantly lower than the mean CC flow void area obtained prior to treatment (Pre-treatment: 0.270 vs Post-treatment: 0.144; p = .0068). In 2 out of 2 patients with longitudinal visual field testing, CC flow voids were spatially associated with visual field defects, and immunosuppressive therapy was associated with reduced CC flow void area and improved visual function.Conclusion: OCTA can detect alterations in choriocapillaris flow. Longitudinal follow-up demonstrates a centripetal restoration of choriocapillaris flow in response to immunosuppressive therapy. OCTA may be a useful adjunct for monitoring and evaluating treatment of PIC.

Repeatability of Optical Coherence Tomography Angiography in Uveitic Eyes.

PURPOSE: To investigate the intravisit repeatability of optical coherence tomography angiography (OCTA) in a cohort of uveitis patients. METHODS: One hundred ten patients were imaged twice per eye, per visit, using the Zeiss Cirrus HD-OCT Model 5000 device. To calculate choriocapillaris flow void area (CC FV) 6 × 6-mm images were used, and 3 × 3-mm images were used to calculate vessel density (VD) and the foveal avascular zone area (FAZ) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Repeatability was measured using Bland-Altman analyses and intraclass correlation coefficients (ICC) with associated coefficient of variation (CV). RESULTS: The level of intravisit repeatability differed across indices ranging from moderate to excellent. CC FV had the highest intravisit repeatability with an ICC of 0.980 (95%CI, 0.966-0.989), a CV of 15.9% and Bland-Altman limits of agreement from -0.398 to 0.411 mm2. DCP FAZ had the lowest intravisit repeatability with an ICC of 0.677 (95%CI, 0.510-0.796), a CV of 17.4% and Bland-Altman limits of agreement from -0.395 to -0.355 mm2. Intraoperator repeatability was excellent across all indices. CONCLUSIONS: This study demonstrates that OCTA is a reliable tool to quantitatively assess specific indices of vascular structure in uveitis patients with good intravisit repeatability. However, the range of variability for each index should be taken into account when evaluating clinically meaningful changes. TRANSLATIONAL RELEVANCE: The repeatability of the metrics we have described has implications in supporting the development of OCTA-derived quantitative assessments of the retinal and choroidal vasculature in uveitis patients as potential imaging biomarkers.

Desmin deficiency is not sufficient to prevent corneal fibrosis.

The type III intermediate filament (IF) proteins vimentin and desmin are sequentially overexpressed in stromal myofibroblasts over the period when fibrosis sets in after corneal injury. Prior findings have revealed vimentin-deficient mice are significantly protected from corneal fibrosis after alkali injury, which has implicated this IF protein as an important regulator of corneal fibrosis. It has remained as yet unproven whether desmin contributes in any significant manner to corneal fibrosis. Here we have employed desmin-deficient (Des KO) mice in the corneal alkali injury model and show that injured Des KO mice develop fibrosis and show similar levels of corneal opacity at 14 days post-injury as wild type (WT) mice and retain this phenotype even at 30d post injury. Des KO corneas from injured mice show upregulation of vimentin and alpha-smooth muscle actin expression to equivalent levels as WT corneas, illuminating that desmin deficiency does not interfere with myofibrobast differentiation. Employing the small molecule withaferin A (WFA), an inhibitor of vimentin, we show that WFA treatment causes the decrease in steady state levels of vimentin and serine 38 phosphorylated vimentin, the latter a biomarker associated with corneal fibrosis, and improved corneal clarity through blockade of myofibroblast differentiation. To investigate further the mechanism of fibrosis in desmin deficiency, we examined keratin 8 expression in the epithelium, and found reduced levels of this cytokeratin in injured Des KO corneas compared to WT corneas. This finding also corroborates the decrease of cell proliferation in injured Des KO corneas compared to that in WT corneas. The fibrotic phenotype of Des KO corneas also features abundant vascularization, further exemplifying the magnitude of corneal pathology. Together, these findings illuminate that desmin does not contribute significantly to corneal fibrosis in this injury model.

Treatment challenges in an atypical presentation of tubulointerstitial nephritis and uveitis (TINU).

PURPOSE: To describe an atypical presentation of Tubulointerstitial Nephritis and Uveitis (TINU), with challenges in treatment course. OBSERVATIONS: A 12-year-old Hispanic female presented to the National Eye Institute's Uveitis clinic with bilateral blurred vision, red eyes and photophobia, not responsive to topical steroids. On exam, she had bilateral severe panuveitis with areas of subretinal fluid. During her evaluation, she was noted to have elevated serum creatinine. A kidney biopsy confirmed the presence of severe tubulointerstitial nephritis and interstitial fibrosis. She was treated with oral steroids with excellent resolution of symptoms and subretinal fluid. She continued to have anterior segment flares with attempts to taper oral prednisone which lead to treatment with multiple immunomodulatory agents. Associated hypertension and kidney damage complicated the choice of a secondary immunosuppressive agent. CONCLUSIONS AND IMPORTANCE: Although rare, TINU can present as panuveitis with choroidal involvement which may or may not be preceded by tubulointerstitial nephritis. A renal biopsy is required for definitive diagnosis, but abnormal urinalysis or renal function should raise suspicion for TINU.