C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.

Purpose: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters. Methods: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters. Results: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023). Conclusion: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.

Diagnostic and Management Strategies of Tubulointerstitial Nephritis and Uveitis Syndrome (TINU): Current Perspectives.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disease with unclear pathogenesis but probably related to a combination of genetic predisposition and environmental triggers. Diagnosis is challenging due to the asynchronous onset of renal and ocular symptoms, and it is necessary to exclude other causes of nephritis and uveitis. It affects both sexes, with an overall predominance of females and a median age of onset of 15 years. TINU syndrome is characterized by bilateral, non-granulomatous anterior uveitis and tubulointerstitial nephritis, which can cause acute renal failure in severe cases. Several triggers have been identified including concurrent infections, medications, or endocrine diseases. The diagnosis of TINU is mainly based on clinical and analytical findings, and although urinary ß2-microglobulin is a useful parameter no specific diagnostic test is available. Current perspectives intend to facilitate its diagnosis identifying susceptibility HLA genotypes, serologic markers and imaging tools to avoid renal biopsy. Treatment options for TINU syndrome include corticosteroids, immunosuppressive agents, and intravenous immunoglobulins, but relapses are frequent, and management can be challenging. The purpose of this review is to provide an updated summary of the diagnostic and treatment strategies of TINU syndrome, helping clinicians recognize and manage this rare autoimmune disorder.

Demystifying Ocular Syphilis - A Major Review.

Syphilis, caused by the spirochaete, Treponema pallidum, continues to be a public health challenge globally with its rates steadily increasing in the past few years. The disease is transmitted through small breaks in the skin during sexual contact, or via congenital transmission in utero, either across the placenta or by contact with an active genital lesion during delivery. Estimated 5.7-6 million new cases are detected every year worldwide in the 15-49 years age group. An increased incidence has been reported in most populations with particular clusters in special groups like men who have sex with men, female sex workers, and their male clients. Ocular syphilis has a varied presentation and is considered a great mimicker in all cases of uveitis. The laboratory diagnosis of syphilis is predominantly based on serological tests including TPHA and VDRL. Parenteral penicillin is the cornerstone of treatment for all stages of ocular syphilis.

Clinical Features and Outcomes of Tubulointerstitial Nephritis and Uveitis Syndrome in Spain and Portugal: The IBERTINU Project.

PURPOSE: To assess the clinical features, management and prognosis of patients diagnosed with tubulointerstitial nephritis and uveitis (TINU) syndrome in Spain and Portugal. METHODS: Retrospective multicenter study, which included all patients diagnosed with TINU syndrome managed in 15 uveitis referral centers from Spain and Portugal. RESULTS: Forty-eight subjects with a mean age at diagnosis of 25.0 [14.8; 49.5] years were included. Both eyes were affected in 43 patients (89.6%). The visual outcome was favorable, but immunosuppressive systemic therapy (IST) was needed in 26 (54.16%) due to relapses. Renal function normalized in 35 patients (72.9%). HLA-DQB1*05 was the most common genetic typing (57.1%). The mean follow-up time was 22.5 [11.0; 48.0] months. CONCLUSIONS: Both visual and renal outcomes were favorable, although IST was frequently used. TINU is under- diagnosed, so further prospective studies would provide more knowledge about its recognition and management. EXPERT OPINION: TINU Syndrome is underdiagnosed because ocular and renal disease are asynchronous. Outcomes are favorable so it has to be highly suspected in cases of bilateral anterior uveitis. According to literature and our experience, systemic immunosuppressive therapy is often required because of ocular relapses.This study adds to the previous knowledge that HLA-DQB1*05 could be an important HLA type amongst the TINU Syndrome Iberian population. HLA typing should be assessed in these patients in order to describe its phenotype-genotype relationship better. A considerable number of patients in our series were diagnosed in their sixties, so TINU Syndrome should also be suspected in elderly patients.

Outcome Measures for Disease Monitoring in Intraocular Inflammatory and Infectious Diseases (OCTOMERIA): Understanding the Choroid in Uveitis with Optical Coherence Tomography (OCT).

PURPOSE: To compare imaging modalities for the choroid of the eye, and evaluate various choroidal changes in uveitides entities. METHODS: A comprehensive systematic literature review was conducted looking at current imaging modalities available to assess choroid architecture and commonly used parameters available to qualify and quantify choroidal changes, before looking at specific uveitides entities with choroidal involvement which have been broadly separated into non-infectious and infectious in etiology. RESULTS: We describe the various modalities currently available to evaluate the choroid of the eye such as Ultrasound B Scan, ICGA, and OCT. Choroidal changes in various ocular and systemic diseases such as Behcet's Disease, Sarcoidosis, Syphillis, Tuberculosis, and many more have been reported and published. CONCLUSION: Multiple choroidal tomographic and angiotomographic findings have been demonstrated for evaluation in uveitis. These findings can manifest in multiple ocular and systemic diseases, and can be illustrated using the various imaging modalities at present. Future advancements in choroidal imaging would help to adapt these findings into parameters for clinical practice to properly evaluate these ocular and systemic diseases.

Vascular retinal findings after COVID-19 vaccination in 11 cases: a coincidence or consequence?

PURPOSE: The primary purpose of this study was to assess vascular retinal findings temporally related to COVID-19 vaccination. With greater information regarding all possible future adverse events, we hope to understand the real dimension and relevance of what was presented. METHODS: Eleven patients with visual complaints after COVID-19 vaccination were enrolled. Data on the following were included: age, sex, vaccine, time of symptom onset, systemic findings, medical history, best-corrected visual acuity, and ocular findings by slit-lamp biomicroscopy as well as multimodal retinal imaging (color fundus, red-free photography, spectral-domain optical coherence tomography, optical coherence tomography angiography, and fluorescein-angiography). Inclusion criteria were the presence of ophthalmologic signs within 30 days after the first or second dose of any COVID-19 vaccine. RESULTS: Of 11 patients, five had arterial occlusion (45.4%), four had venous occlusion (36.4%), and two (18.2%) had nonspecific vascular alterations suggestive of retinal ischemia such as cotton-wool spots. The mean age was 57 (SD = 16; range: 27-84) years. The mean time of symptoms onset was 10 (SD = 5.4; range: 3-16) days. Nine patients were female (81.8%). Systemic risk factors were observed in 36.4% of patients. Two patients had both neurological and visual symptoms, with arterial occlusion. Overall, 36.4% patients had COVID-19 in the previous year. Seven patients (63.6%) received ChAdOx1 nCoV-19 (AZD1222) vaccine. CONCLUSIONS: Our data suggest that retinal events temporally related to COVID-19 vaccination are possible but are very rare. The relationship of these events with post-COVID-19 vaccination warrants further attention to derive a meaningful conclusion.

CHARACTERIZING COVID-19-RELATED RETINAL VASCULAR OCCLUSIONS: A Case Series and Review of the Literature.

PURPOSE: To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions. METHODS: Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography. RESULTS: Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) µm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 µm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series. CONCLUSION: Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.

Adalimumab in Elderly Patients with Non-Infectious Uveitis. Safety and Efficacy.

Purpose: To assess the efficacy and safety of adalimumab in elderly patients with noninfectious uveitis (NIU).Methods: An observational, retrospective, multicenter study was done. Changes in best-corrected visual acuity (BCVA), inflammatory activity parameters, central retinal thickness (CRT), and the occurrence of adverse events (AE) developed during follow-up were recorded.Results: A total of 82 eyes from 41 patients 60 years of age and older with noninfectious uveitis treated with adalimumab were included. A significant improvement in BCVA (71.5 to 75.4 letters, p = .001) and in CRT (311.1 µm to 265 µm, p = .001) was observed. Moreover, a significant decrease from baseline in the rate of patients with anterior chamber cell (ACC) >0+ (34.6% to 5.7%, p = <0.001) or vitreous haze>0+ (21.3% to 4.3%, p = .002) was determined. AEs were observed in 11 patients (26.8%).Conclusion: Adalimumab can be safe and efficacious for the treatment of NIU in patients 60 years of age and older.

Paraneoplastic Focal Outer Retinitis and Optic Neuropathy in a Patient with Small Cell Lung Carcinoma and Anti-CRMP5, Anti-HU and Anti-Amphiphysin Antibodies.

Our aim is to describe clinical and optical coherence tomographic features of acute paraneoplastic focal outer retinitis associated with optic neuropathy in a patient diagnosed with small cell lung carcinoma. Bilateral focal outer retinitis, bilateral optic disc oedema and vitritis were identified in a patient with progressive bilateral visual loss and ataxia. Spectral domain optical coherence tomography (SD-OCT) revealed various extents of granular hyperreflectivity and atrophy of the macular outer retinal layers. Serum and cerebrospinal fluid positivity for anti-CRMP5, anti-HU and anti-amphiphysin antibodies intensified the search for an underlying malignancy, and a small cell lung carcinoma (SCLC) was finally diagnosed. Local and oral steroids along with systemic chemotherapy and radiotherapy achieved cancer remission and partial recovery from the ophthalmic manifestations. Focal outer retinitis associated with optic disc oedema and antibody positivity facilitated the diagnosis of SCLC in a localized stage. SD-OCT allowed the characterization of this entity, expanding the spectrum of paraneoplastic ophthalmological syndromes.

INTERNAL LIMITING MEMBRANE PEELING VERSUS NONPEELING TO PREVENT EPIRETINAL MEMBRANE DEVELOPMENT IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A Swept-Source Optical Coherence Tomography Study With a New Postoperative Classification System.

PURPOSE: To determine whether internal limiting membrane peeling in primary rhegmatogenous retinal detachment prevents epiretinal membrane (ERM) development. Secondarily, we propose a classification system for postoperative ERMs. METHODS: Retrospective, interventional, comparative case series. Consecutive eyes with primary rhegmatogenous retinal detachment (n = 140) treated by a single surgeon. The presence of postoperative ERMs was assessed with swept-source optical coherence tomography. RESULTS: An ERM was detected in 26 eyes (46.4%) in the nonpeeling group and in one eye (1.8%) in the internal limiting membrane peeling group (P ≤ 0.001). The median visual acuity significantly improved in both groups (P ≤ 0.001). Inner retinal dimples were observed in 41.1% of eyes in the internal limiting membrane peeling group versus 0% in the nonpeeling group (P ≤ 0.001), and they were not correlated with visual acuity (r = 0.011; P = 0.941). Based on swept-source optical coherence tomography findings, we identified three different types of ERMs: 7 (26.9%) were classified as Type 1, 12 (46.1%) as Type 2, and 7 (26.9%) as Type 3. Superficial retinal plexus deformations observed on optical coherence tomography angiography and en face images were detected in 100% of Type 3 ERMs, 41.6% of Type 2, and 0% of Type 1 (χ = 14.3; P = 0.001). Interestingly, all of the patients who presented these alterations also had metamorphopsia. CONCLUSION: Internal limiting membrane peeling in primary rhegmatogenous retinal detachment seems to prevent postoperative ERM development. Swept-source optical coherence tomography analysis is helpful to define and classify different types of ERMs and to establish the surgical indication for their removal.