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.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.

PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide. DESIGN: Multicenter national nAMD database observational study. SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification. MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions. CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Non-invasive biomarkers for close activity monitoring in birdshot chorioretinitis: Optical coherence tomography angiography and beyond.

PURPOSE: The purpose of the study was to identify non-invasive imaging biomarkers potentially useful for close activity monitoring in birdshot chorioretinitis (BSCR). METHODS: Cross-sectional study of BSCR eyes included as per Levinson's and/or SUN criteria. Eyes were blindly classified into active or inactive groups per clinical inflammatory parameters, ultra-widefield (UWF) pseudocolour images, UWF fluorescein angiography (FA) and macular optical coherence tomography (OCT) cube. Qualitative and quantitative OCT and OCT-angiography (OCT-A) parameters at the fundus, superonasal and inferonasal fields were compared between active and inactive eyes. RESULTS: Thirty consecutive BSCR patients (60 eyes) were analysed. 28 eyes (46.66%) were from women and the overall mean age was 59.7 ± 12.3 years. Active eyes showed an abnormal retinal thickening at inferonasal field (nasal retinal thickness) and a higher averaged thickened retinal index (ATRI) (72.36 active vs. 20.12 inactive, p < 0.0001). A significant moderate correlation was observed between ATRI and FA scores (r = 0.259, p = 0.022). Macular vascular loops were more frequent in the superficial vascular plexus of OCT-A in the active eyes (p = 0.028). The vascular perfusion index tended to be higher in all subfields of active eyes but did not reach statistical significance. CONCLUSION: Multimodal imaging could be key to discerning activity in BSCR eyes. Higher ATRI and the presence of vascular loops in the superficial plexus are potential non-invasive activity biomarkers for the close monitoring of BSCR.

Predictive value of retinal atrophy for cognitive decline across disease duration in multiple sclerosis.

BACKGROUND: We investigated the association between changes in retinal thickness and cognition in people with MS (PwMS), exploring the predictive value of optical coherence tomography (OCT) markers of neuroaxonal damage for global cognitive decline at different periods of disease. METHOD: We quantified the peripapillary retinal nerve fibre (pRFNL) and ganglion cell-inner plexiform (GCIPL) layers thicknesses of 207 PwMS and performed neuropsychological evaluations. The cohort was divided based on disease duration (≤5 years or >5 years). We studied associations between changes in OCT and cognition over time, and assessed the risk of cognitive decline of a pRFNL≤88 µm or GCIPL≤77 µm and its predictive value. RESULTS: Changes in pRFNL and GCIPL thickness over 3.2 years were associated with evolution of cognitive scores, in the entire cohort and in patients with more than 5 years of disease (p<0.01). Changes in cognition were related to less use of disease-modifying drugs, but not OCT metrics in PwMS within 5 years of onset. A pRFNL≤88 µm was associated with earlier cognitive disability (3.7 vs 9.9 years) and higher risk of cognitive deterioration (HR=1.64, p=0.022). A GCIPL≤77 µm was not associated with a higher risk of cognitive decline, but a trend was observed at ≤91.5 µm in PwMS with longer disease (HR=1.81, p=0.061). CONCLUSIONS: The progressive retinal thinning is related to cognitive decline, indicating that cognitive dysfunction is a late manifestation of accumulated neuroaxonal damage. Quantifying the pRFNL aids in identifying individuals at risk of cognitive dysfunction.

Progression of Retinal Ganglion Cell and Nerve Fiber Layer Loss in Spinocerebellar Ataxia 3 Patients.

Spectral domain optical coherence tomography (SD-OCT) allows noninvasive measurements of retinal neuron layers. Here, we evaluate the relationship between clinical features and anatomical SD-OCT measurements in patients with spinocerebellar ataxia type 3 (SCA3) and how they change with time. A retrospective review was conducted on SCA3 patients. Clinical variables such as disease duration, number of CAG repeats, and the Scale for the Assessment and Rating of Ataxia (SARA) score were correlated with SD-OCT measurements, including retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, macular volume (MV), and central macular thickness (CMT). Seventeen SCA3 patients with an average follow-up of 44.9 months were recruited. Clinical features with significant baseline correlations with SD-OCT measurements included disease duration (CMT r = - 0.590; GCC r = - 0.585), SARA score (CMT r = - 0.560; RNFL r = - 0.390), and number of CAG repeats (MV r = - 0.552; RNFL r = - 0.503; GCC r = - 0.493). The annual rate of change of the SARA score during follow-up was associated with that of both the MV (r = - 0.494; p = 0.005) and GCC thickness (r = - 0.454; p = 0.012). High disability (stages 2 and 3) was independently inversely associated with the annual change in MV (ß coefficient - 17.09; p = 0.025). This study provides evidence of an association between clinical features and objective anatomical measurements obtained by SD-OCT in SCA3 patients. MV and GCC thickness could serve as potential biomarkers of disease severity, as their rates of decrease seem to be related to a worsening in the SARA score. These findings highlight the potential of SD-OCT as a noninvasive tool for assessing disease severity and progression in SCA3 patients.

Ocular related emergencies in Spain during the COVID-19 pandemic, a multicenter study.

PURPOSE: To evaluate ophthalmological emergencies (OE) during the COVID-19 pandemic comparing them with the same period of the previous year. METHODS: Retrospective observational study of all OE visits in four tertiary hospitals in Spain comparing data from March 16th to April 30th, 2020 (COVID-19 period) and the same period of 2019 (pre-COVID-19 period). Severity of the conditions was assessed following Channa et al. publication. Data on demographics, diagnosis and treatments were collected from Electronic Medical Records. RESULTS: During lockdown, OE significantly declined by 75.18%, from 7,730 registered in the pre-COVID-19 period to 1,928 attended during the COVID-19 period (p < 0.001). In 2019, 23.86% of visits were classified as emergent, 59.50% as non-emergent, and 16.65% could not be determined. In 2020, the percentage of emergent visits increased up to 29.77%, non-emergent visits significantly decreased to 52.92% (p < 0.001), and 17.31% of the visits were classified as "could not determine". During the pandemic, people aged between 45 and 65 years old represented the largest attending group (37.89%), compared to 2019, where patients over 65 years were the majority (39.80%). In 2019, most frequent diagnosis was unspecified acute conjunctivitis (11.59%), followed by vitreous degeneration (6.47%), and punctate keratitis (5.86%). During the COVID-19 period, vitreous degeneration was the first cause for consultation (9.28%), followed by unspecified acute conjunctivitis (5.63%) and punctate keratitis (5.85%). CONCLUSIONS: OE visits dropped significantly during the pandemic in Spain (75.18%), although more than half were classified as non-urgent conditions, indicating a lack of understanding of the really emergent ocular pathologies among population.

Simultaneous pars plana vitrectomy, panretinal photocoagulation, cryotherapy, and Ahmed valve implantation for neovascular glaucoma.

AIM: To describe and evaluate the efficacy of Ahmed glaucoma valve implantation (AGV) combined with pars plana vitrectomy (PPV) in a single surgical act for the treatment of advanced neovascular glaucoma (NVG). METHODS: Retrospective observational case series included 51 eyes from 50 patients with severe NVG treated with PPV, AGV, and panretinal photocoagulation and/or cryotherapy in a single surgical act during a 13-year period (2005-2018). Preoperative, intraoperative and postoperative data at day 1 and months 1, 3, 6, 21, and 24 were systematically collected. Definition of surgical success was stablished at IOP between 6 and 21 mm Hg with or without topical treatment. RESULTS: Main indications for surgery were NVG secondary to proliferative diabetic retinopathy (39.2%) and central retinal vein occlusion (37.3%). Mean (±SD) preoperative IOP was 42.0±11.2 mm Hg decreasing to 15.5±7.1 mm Hg at 12mo and 15.8±9.1 mm Hg at 24mo of follow up. Cumulative incidence of success of IOP control was 76.0% at first postoperative month, reaching 88.3% at 6mo. Prevalence of successful IOP control at long term was 74.4% at 12mo and 71.4% at 24mo. Eye evisceration for unsuccessful NVG management was required in 1 case (2.0%). CONCLUSION: Combination of AGV implantation and PPV in a single act may be a suitable option for severe forms of NVG in a case-by-case basis for effective IOP control and a complete panretinal photocoagulation.

Orbital TFE3-Rearranged Perivascular Epithelioid Cell Tumor: A Case Report and Review of the Literature.

ABSTRACT: Perivascular epithelioid cell tumors (PEComas) are infrequent mesenchymal neoplasms that have particular histological and immunohistochemical features. Only a few cases have been described in the eye and orbit. This report presents a 28-year-old man who consulted for a painless left orbital mass. With the presumptive diagnosis of cavernous hemangioma, a surgical excisional biopsy was performed. Histopathological examination showed a well-delimited tumor composed of epithelioid cells with an eosinophilic cytoplasm and oval nucleus. The tumor cells stained diffusely for HMB-45 and transcription factor E3 (TFE3) and were focally positive for actin. There was no reactivity to S100 or desmin. Genetic testing revealed a TFE3 rearrangement. Based on these results, an extremely rare orbital TFE3-rearranged PEComa was diagnosed. Although no recurrence was seen at last follow-up, a review of the literature shows experience is limited regarding orbital PEComas and their malignant potential. Further research is needed to establish management guidelines, their association with the tuberous sclerosis complex, and the role of genetic mutations such as TFE3 rearrangement.

In Vivo Molecular Changes in the Retina of Patients With Multiple Sclerosis.

Purpose: Raman spectroscopy allows molecular changes to be quantified in vivo from the tissues like the retina. Here we aimed to assess the metabolic changes in the retina of patients with multiple sclerosis (MS). Methods: We built a Raman spectroscopy prototype by connecting a scanning laser ophthalmoscope to a spectrophotometer. We defined the spectra of 10 molecules participating on energy supply, axon biology, or synaptic damage, which have been shown to be altered in the brain of patients with MS: cytochrome C, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NADH), N-acetyl-aspartate (NAA), excitotoxicity, glutamate, amyloid ß (Aß), τ and α-synuclein (SNCA), phosphatidyl-ethanolamine, and phosphatidyl-choline. We studied these molecules in a prospective cohort of patients with MS, either in the chronic phase or during relapses of acute optic neuritis (AON). Results: Significant changes to all these molecules were associated with age in healthy individuals. There was a significant decrease in NADH and a trend toward a decrease in NAA in patients with MS, as well as an increase in Aß compared with healthy controls. Moreover, NADH and FAD increased over time in a longitudinal analysis of patients with MS, whereas Aß diminished. In patients with acute retinal inflammation due to AON, there was a significant increase in FAD and a decrease in SNCA in the affected retina. Moreover, glutamate levels increased in the affected eyes after a 6-month follow-up. Conclusions: Alterations of molecules related to axonal degeneration are observed during neuroinflammation and show dynamic changes over time, suggesting progressive neurodegeneration.

XEN45 real-life evaluation: Survival analysis with bleb needling and major revision outcomes.

PURPOSE: To evaluate real-life outcomes of XEN45 stent surgery including bleb needling (BN) and surgical bleb revision (SBR). METHODS: Retrospective analysis of all XEN45 gel stents implanted in a tertiary glaucoma center with a minimum follow-up of 6 months. The main outcomes were intraocular pressure (IOP), the number of glaucoma medications, postoperative maneuvers like BN, and subsequent SBR. Success was defined as IOP ⩽ 18 and 20% reduction (criterion A), ⩽15 and 25% reduction (criterion B), and ⩽12 mmHg and 30% reduction (criterion C) reached with (qualified) or without (complete) medications at the last visit. Complete failure was defined as additional glaucoma surgery, loss of light perception, or sight-threatening complications. Multivariable Cox regression and Kaplan-Meier survival estimates tests were performed. RESULTS: Fifty-eight eyes with either stand-alone or combined Phaco-XEN surgery were included. Complete success by the different definitions was 50.0% (95% confidence interval, 5.8%-84.5%) (A), 50.0% (5.8%-84.5%) (B), and 25% (0.9%-66.5%) (C) whereas qualified success was 38.3% (1.6%-80.1%), 31.7% (2.0%-71.4%), and 0%, respectively, at the 24-months visit. 30% of cases underwent BN with 5-Fluorouracil, and SBR was performed in 17.5% of eyes. Low IOP levels at 1-month and early BN were significantly associated with success. The highest chance of failure was achieved in the combined Phaco-XEN group undergoing SBR. CONCLUSIONS: In our real-life setting, the first month IOP was associated with greater success rates. Although BN obtained improved IOP values, SBR was associated with a greater bleb survival in the stand-alone XEN group. Both BN and SBR had poor outcomes in the combined Phaco-XEN group.

Late Onset Macular Oedema in a Patient with Multiple Sclerosis Treated with Fingolimod.

Macular oedema is a rare complication of fingolimod treatment. It usually presents within 3-4 months, but occasionally presents later. It can resolve without treatment despite continuation of fingolimod treatment. Herein we report a case of very late onset macular oedema in a 49-year-old woman with multiple sclerosis treated with fingolimod for 7 years. The patient presented with blurred vision in both eyes with visual acuities of 20/32 in her right eye and 20/25 in her left eye. She had macular oedema, that without discontinuing fingolimod treatment, resolved after 1 month.

Eye bank and theatre factors for positive microbiological culture of corneoscleral rim and cornea storage medium in the real-world.

OBJECTIVES: To evaluate microbiological culture rate and positivity of corneoscleral rim and cornea storage media as well as possible risk factors for contamination with real-world data. METHODS: Data of consecutive cornea donors implanted in the reference centre from January 2013 to January 2018 were reviewed. Information about cornea characteristics (donor demographic data, endothelial cell density, type of cornea conservation, days of storage, and precut vs full-thickness tissue), and microbiological culture information (corneoscleral rim vs storage sample, positive result) were statistically analysed. RESULTS: During the study period, 1369 corneas (737 donors) were implanted. Cultures were performed in 76.8% (n = 1052) of them and were positive in 3.2% of cases, mainly bacteria (84.4%). Corneas preserved in hypothermia represented 61.8% of all positive microbiology results (p < 0.001). Other analysed risk factors did not reach statistically significant association with microbiological positivity. None of the 34 cases with positive microbiological cultures reported ocular infection for the recipients in at least 6 months' follow-up. CONCLUSIONS: Microbiological tests rate in real-world practice are high despite not being compulsory. Organotypic cultured corneas showed a statistically less positivity in corneoscleral and storage medium than hypothermic ones, resulting in another advantage of this kind of cornea storage. Although precut corneas are thought to present less microbiological positivity, a statistically significant association was not found in the present study.

Postoperative treatment compliance rate and complications with two different protocols after pterygium excision and conjunctival autografting.

AIM: To evaluate compliance rate to pterygium postoperative treatment with two different protocols. METHODS: Review of clinical data of patients submitted to pterygium excision and conjunctival autografting in a single centre (and a single surgeon) in Barcelona between March 2014 and December 2017. Initial postoperative protocol (protocol 1) consisted of 4 months of topical steroids in a tapering fashion. Protocol 2 consisted of topical steroids tapered over 5 weeks. Compliance rate, complications and clinical outcomes were evaluated, and statistical comparisons were made. RESULTS: 120 surgeries were performed in 99 patients. Protocol 1 was applied in 63 cases and the next 57 followed protocol 2. Compliance with protocol 1 (57.6%) was lower than with protocol 2 (84.9%) (p = 0.002). Intraoperative complications (graft tear, corneal thinning, corneal perforation and bleeding) were found in 10 cases of protocol 1 and three cases of protocol 2, p = 0.08. Postoperative complications (graft dislocation, graft haematoma, ocular hypertension and recurrence) were found in 31 cases of protocol 1 (46.2%) and eight cases of protocol 2 (14%), p = 0.001. Six weeks after surgery, ocular hypertension was detected in eight cases corresponding to protocol 1 (13.6%) and two cases of protocol 2 (3.8%), p = 0.099. Recurrence rate during first year was higher in protocol 1 (26.3%) compared to protocol 2 (7.6%), p = 0.011. No cases of visual acuity worsening or infection were registered. CONCLUSION: Protocol 2 has shown to have higher compliance rate than protocol 1 and less postoperative complications, proving to be a safe and effective postoperative treatment after pterygium surgery.