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.

New proposal for a multimodal imaging approach for the subclinical detection of hydroxychloroquine-induced retinal toxicity in patients with systemic lupus erythematosus.

OBJECTIVE: To compare multimodal structural and functional diagnostic methods in patients with systemic lupus erythematosus (SLE) treated with hydroxychloroquine, to identify the best complementary approach for detecting subclinical retinal toxicity. METHODS: A cross-sectional, unicentric study was conducted on patients with SLE treated with hydroxychloroquine. Each patient underwent a comprehensive ophthalmic evaluation, comprising structural tests (spectral-domain optical coherence tomography (SD-OCT), en face OCT, en face OCT angiography (OCTA), fundus autofluorescence (FAF)) and functional tests (automated perimetry for visual field (VF) testing, multifocal electroretinography (mfERG)). A diagnosis of macular toxicity required the presence of abnormalities in at least one structural and functional test. The Kappa Concordance Index was used to assess the concordance among the different tests in detecting potential macular toxicity-associated alterations. RESULTS: Sixty-six patients with SLE (132 eyes) were consecutively enrolled. Four (6.1%) patients developed subclinical hydroxychloroquine-induced retinal toxicity without visual acuity impairment. The proportion of abnormal results was 24% for both en face OCT and en face OCTA. Regarding functional analysis, VF was less specific than mfERG in detecting subclinical retinal toxicity (VF specificity 47.5%). En face OCT and en face OCTA structural findings showed better concordance, with a kappa index >0.8, and both identified the same cases of toxicity as FAF. CONCLUSION: Although structural OCT and VF are frequently used to screen for hydroxychloroquine-induced retinal toxicity, our findings suggest that a combination of mfERG, en face OCT and en face OCTA could improve the diagnostic accuracy for subclinical retinal damage. This study emphasises the importance of a multimodal imaging strategy to promptly detect signs of hydroxychloroquine-induced retinal toxicity.

Comparison of intraocular lens tilt after capsular sutured scleral fixation with capsular segments versus uneventful cataract surgery.

PURPOSE: To evaluate and compare intraocular lens (IOL) tilt between uneventful phacoemulsification with in-the-bag IOL implantation and sutured scleral fixation (SSF) of the lens bag with a capsular tension segment (type 6 D / Morcher) using a Sheimpflug camera. SETTING: Clinical Practice, Hospital. Barcelona and A Coruña, Spain. DESIGN: Retrospective, comparative multicenter study. METHODS: IOL tilt was compared between patients who underwent sutured scleral fixation with a capsular tension segment in a single eye (SSF group, n = 15) with patients who underwent uneventful IOL implantation (control group, n = 12) that were matched by biometric measurements. Post-operative refractive accuracy of biometric formulas by means of mean absolute error (MAE) was also reported. All patients underwent a general ophthalmic evaluation, anterior segment photography, and postoperative optical biometry (Zeiss IOLMaster® 500). In addition, IOL tilt was measured with a Scheimpflug camera (Pentacam R, Oculus Optikgerate Gmbh). RESULTS: Mean vertical tilt was similar in both groups (2.20+/-2.47° SSF vs 1.97 +/- 1.79° control; p = 0.836) but mean horizontal tilt tended to higher values in the SSF series (2.09 +/- 2.74° vs 0.94 +/- 1.17°; p = 0.139). Considering post-operative refractive error in diopters by MAE calculations, there was an underestimation of IOL power in the SSF group which was only statistically significant for Barrett Universal II (1.07 vs 0.32; p = 0.028) and Hill-RBF (0.95 vs 0.26; p = 0.024) formulas, but not for SRK/T (0.99 vs 0.42; p = 0.285) and Kane (0.96 vs 0.33; p = 0.083). CONCLUSION: Sutured scleral fixation of capsular tension segments in the presence of zonular instability does not seem to induce clinically significant IOL tilt compared to uneventful cataract extraction cases.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

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.

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.

Intravitreal fluocinolone acetonide implant for the treatment of persistent post-surgical cystoid macular edema in vitrectomized eyes.

Cystoid macular edema (CME) is the most common cause of decreased visual acuity after both vitrectomy and cataract surgery. Various strategies have been used for its treatment, such as intravitreal corticosteroids. The intravitreal fluocinolone acetonide implant (Iluvien®) is approved for the treatment of persisting diabetic macular edema and for the prevention of recurrence of non-infectious uveitis affecting the posterior segment. There are very few reports about its off-label use for post-surgical CME. We present four clinical cases of post-surgical CME (three following vitrectomy and one following cataract surgery in a vitrectomized eye 2 years ago). All of them had been previously treated with an average of four injections of intravitreal dexamethasone implant (Ozurdex®), with repeated recurrence of CME. After treatment with Iluvien, three cases showed improvement of both visual acuity and macular anatomy, with resolution of the macular edema. One patient required additional treatment with Ozurdex during follow-up, further improving CME. Two of the cases required topical pressure lowering treatment, and none required filtering surgery. Iluvien could be an effective therapeutic option for persistent non-diabetic macular edema after vitrectomy or cataract surgery refractory to other intravitreal therapies, with the benefit of being able to provide longer recurrence-free periods.

Preclinical ocular changes in systemic lupus erythematosus patients by optical coherence tomography.

OBJECTIVE: The aim of the present study was to detect preclinical changes in SLE patients in retinal microvascularization or retinal and optical nerve structure by optical coherence tomography. METHODS: This cross-sectional, single-centre study aimed to describe structural changes [macular and retinal nerve fibre layer (RNFL) thickness] by structural spectral-domain optical coherence tomography (SD-OCT) and perifoveal vascular [vessel density (VD) and vascular perfusion (VP) and foveal avascular zone (FAZ) structural parameters] findings by OCT angiography (OCTA) in 78 SLE patients and 80 healthy volunteers. In addition, we analysed their association with clinical and laboratory parameters, medications received, disease duration, and SLE activity and damage. RESULTS: Structural parameters by SD-OCT and perifoveal vascular parameters by OCTA were decreased in SLE patients compared with controls. OCTA parameters (VD, VP and FAZ circularity) and macular thickness were also decreased in patients with longer disease duration (>10 years). The presence of aPLs was associated with a decreased RNFL thickness, mainly in the inferior quadrants. Patients developing APS also showed decreased RNFL thickness and OCTA flow changes. SD-OCT and OCTA results were not associated with disease activity. Foveal structural parameters were lower in patients with higher damage score. CONCLUSION: SD-OCT and OCTA can detect preclinical structural and microcirculatory changes in SLE patients. Structural and perifoveal vascular macular changes in SLE patients are related to disease duration. Macular structural parameters were impaired in patients with higher disease damage. APS seems to be associated with preclinical damage to the optic nerve and impairment of the perifoveal microvasculature.

Altered retinal structure and function in Spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice. We evaluated the retinal structure and function in five patients with SCA3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using optical coherence tomography (OCT) and electroretinogram (ERG). In the transgenic mice, we further: a) determined the retinal expression pattern of ATXN3 and the distribution of cones and rods using immunofluorescence (IF); and b) assessed the retinal ultrastructure using transmission electron microscopy (TEM). Some patients with SCA3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and showed further thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli. Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with SCA3.

Intravitreal anti-vascular endothelial growth factor injections to treat post-trabeculectomy Swan syndrome.

PURPOSE: To report a case of wound neovascularization (Swan syndrome) one year after trabeculectomy favorably treated with two intravitreal ranibizumab injections. OBSERVATIONS: A 79-year-old woman under coumadin treatment for atrial fibrillation experienced relapsing decreased vision in her left eye due to vitreous hemorrhage. She had had a past history of ocular hypertension corneal decompensation after phacoemulsification that required a Descemet Membrane Endothelial Keratoplasty and a subsequent trabeculectomy. After clearance of the hemorrhage, examination showed neovascularization not in the retina but surrounding the sclerostomy wound of the trabeculectomy, being diagnosed as a Swan syndrome. After two intravitreal injections of ranibizumab, gonioscopy showed complete resolution of the new vessels. No further recurrences have been reported and IOP has remained controlled without glaucomatous changes 7 months after the last injection. Clinical features and patient characteristics are described. CONCLUSION AND IMPORTANCE: Anti-vascular endothelial growth factor intravitreal injections may be a good and safe alternative to manage vitreous hemorrhage secondary to wound neovascularization of the trabeculectomy site.

Creation of a neovascular age-related macular degeneration national database using a web-based platform: Fight Retinal Blindness Spain. Report 1: Visual outcomes.

BACKGROUND: To study the visual outcomes of neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs at national level. METHODS: Multicenter national database of nAMD eyes treated with anti-VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat-and-extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!). RESULTS: 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p = 0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/-3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p = 0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p = 0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%). CONCLUSION: Independent, large-scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real-world international cohorts.

Dexamethasone Implant for Diabetic Macular Oedema: 1-Year Treatment Outcomes from the Fight Retinal Blindness! Registry.

INTRODUCTION: Phase III clinical trials of dexamethasone intravitreal implant for diabetic macular oedema (DMO) have reported significant improvements in visual acuity (VA). Studies evaluating the treatment of DMO in routine clinical practice provide data to identify areas that need improvement. This study evaluated 12-month treatment outcomes of dexamethasone implant for DMO in routine clinical practice. METHODS: Retrospective data analysis of eyes that started dexamethasone implant for DMO from 1 June 2013 to 30 April 2019 in routine clinical practice tracked in the Fight Retinal Blindness! Registry. RESULTS: Of the 4282 eyes (2518 patients) that started DMO treatment in the specified period, 267 (6%) eyes (204 patients) received 454 dexamethasone implant injections. Two-fifths (106 eyes) had received prior treatment for DMO. The mean (95% confidence interval [CI]) VA change at 12 months was 1.8 (- 0.5, 4.2) letters from the mean (standard deviation [SD]) VA of 56.5 (19.8) letters at baseline, with 41% eyes achieving at least 20/40. The mean (95% CI) change in central subfield thickness over 1 year was - 79 (- 104, - 54) µm from a mean (SD) of 459 (120) µm at baseline. Eyes that completed 1 year of follow-up received a median (Q1, Q3) of 2 (1, 2) dexamethasone implants. One-tenth of phakic eyes received cataract surgery while 2% had a pressure response requiring anti-glaucoma medications. CONCLUSIONS: One-year treatment outcomes of dexamethasone intravitreal implant for DMO in routine clinical practice were inferior to those in the clinical trials perhaps because of fewer treatments in clinical practice.

Trends in Corneal Transplantation in a Tertiary Hospital in Brazil.

PURPOSE: The purpose of this study was to analyze the evolving trends of surgical techniques and indications of corneal transplantation (CT) at a tertiary hospital in Brazil. METHODS: The medical records of all patients who underwent CT at the Hospital Oftalmológico de Sorocaba (Sorocaba Eye Hospital) from the Banco de Olhos de Sorocaba (Sorocaba Eye Bank) group in Sorocaba, Brazil, from January 1, 2012, to December 31, 2019, were analyzed. Data regarding age, sex, transplant indication, and surgical technique were collected. RESULTS: A total of 16,250 CTs were performed. There was a statistically significant decreasing trend of keratoconus-related CT ( P < 0.0001), with rates dropping from 41.7% among all CTs in 2012 to 25.5% in 2019. Penetrating keratoplasty, anterior lamellar keratoplasty, and endothelial keratoplasty (EK) accounted for 59.3%, 27.1%, and 7.8% of the CTs performed in 2012 and 33.3%, 16.4%, and 39.9% in 2019, respectively. A statistically significant decreasing trend was observed for penetrating keratoplasty ( P < 0.0001) and anterior lamellar keratoplasty ( P < 0.0001), whereas EK showed a statistically significant increasing trend during the period ( P < 0.0001). Among EKs, Descemet membrane EK increased statistically significantly from 12.8% in 2012 to 74.4% in 2019 ( P < 0.0001). CONCLUSIONS: This study shows relevant evolving trends in indications and preferred CT techniques in a tertiary hospital in Brazil.

C-reactive protein isoforms as prognostic markers of COVID-19 severity.

C-reactive protein (CRP), an active regulator of the innate immune system, has been related to COVID-19 severity. CRP is a dynamic protein undergoing conformational changes upon activation in inflammatory microenvironments between pentameric and monomeric isoforms. Although pentameric CRP is the circulating isoform routinely tested for clinical purposes, monomeric CRP shows more proinflammatory properties. Therefore, we aimed to determine the potential of monomeric CRP in serum as a biomarker of disease severity in COVID-19 patients (admission to intensive care unit [ICU] and/or in-hospital mortality). We retrospectively determined clinical and biological features as well as pentameric and monomeric CRP levels in a cohort of 97 COVID-19 patients within 72h of hospital admission. Patients with severe disease had higher levels of both pentameric and monomeric CRP. However, multivariate analysis showed increased mCRP but not pCRP to be independently associated to disease severity. Notably, mCRP levels higher than 4000 ng/mL (OR: 4.551, 95% CI: 1.329-15.58), together with number of co-morbidities, low lymphocyte count, and procalcitonin levels were independent predictors of disease severity in the multivariate model. Our results show the potential of mCRP levels as a marker of clinical severity in COVID-19 disease.

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 4: Glycated Haemoglobin.

The purpose of this study was to evaluate specifically the relationship between glycated haemoglobin (HbA1c) levels and retinal optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in type 1 Diabetes Mellitus (DM). A total of 478 type 1 DM patients and 115 controls were included in a prospective OCTA trial (ClinicalTrials.gov NCT03422965). Subgroup analysis was performed for controls, no diabetic retinopathy (DM-no DR) and DR patients (DM-DR), and HbA1c levels. OCT and OCTA measurements were compared with HbA1c levels (current and previous 5 years). DM-no DR patients with HbA1c levels >7.5% showed lower VD than DM-DR and controls (20.16 vs. 20.22 vs. 20.71, p < 0.05), and showed a significant correlation between HbA1c levels and FAZc (p = 0.04), after adjusting for age, gender, signal strength index, axial length, and DM disease duration. DM-DR patients with HbA1c > 7.5% presented greater CRT than DM-no DR and controls (270.8 vs. 260 vs. 251.1, p < 0.05) and showed a significant correlation between HbA1c and CRT (p = 0.03). In conclusion, greater levels of HbA1c are associated with OCTA changes in DM-no DR patients, and with structural OCT changes in DM-DR patients. The combination of OCTA and OCT measurements and HbA1c levels may be helpful to identify patients at risk of progression to greater stages of the diabetic microvascular disease.

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.

Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H.

Age-related macular degeneration (AMD) heads the list of legal blindness among the elderly population in developed countries. Due to the complex nature of the retina and the variety of risk factors and mechanisms involved, the molecular pathways underlying AMD are not yet fully defined. Persistent low-grade inflammation and oxidative stress eventually lead to retinal pigment epithelium dysfunction and outer blood-retinal barrier (oBRB) breakdown. The identification of AMD susceptibility genes encoding complement factors, and the presence of inflammatory mediators in drusen, the hallmark deposits of AMD, supports the notion that immune-mediated processes are major drivers of AMD pathobiology. Complement factor H (FH), the main regulator of the alternative pathway of the complement system, may have a key contribution in the pathogenesis of AMD as it is able to regulate both inflammatory and oxidative stress responses in the oBRB. Indeed, genetic variants in the CFH gene account for the strongest genetic risk factors for AMD. In this review, we focus on the roles of inflammation and oxidative stress and their connection with FH and related proteins as regulators of both phenomena in the context of AMD.

Amniotic membrane extract eye drops for ocular surface diseases: use and clinical outcome in real-world practice.

PURPOSE: To study the indications and clinical outcomes, in a real-word setting, of amniotic membrane extract eye drops (AMEED) use for ocular surface disease (OSD). METHODS: A retrospective study of patients treated with topical AMEED between January 2018 and January 2020 was conducted. Patients were classified in two groups according to specific OSD-dry eye disease (DED) and wound healing delay (WHD) groups. Demographics, comorbidities, treatment duration and clinical outcomes were analysed. RESULTS: A total of 50 eyes of 36 patients with or without previous treatments were included. Patients in the DED group presented more systemic comorbidities (83 vs 22%; p < 0.001) and spent more mean time under AMEED treatment (10 vs 7.2 months average) than the WHD group (p = 0.0104). In four patients, long-term treatment (more than 24 months) was reported. Global similar symptomatic improvement was reported for both groups (DED 88.9% vs WHD 100%; p = 0.486), with the WHD group especially consisting in general relief (78%) and the DED group reporting more pain improvement (44%) (p = 0.011). Regarding patients with autologous serum as a previous treatment, no statistical differences were found in subjective or objective improvement. An overall success was achieved in 94.4% of the cases and no adverse events were found. CONCLUSION: AMEED administration is a promising mean to treat OSD such as dry eye, persistent epithelial defect and corneal ulcers. Although AMEED may be effective in the treatment of severe DED and persistent epithelial defect or corneal ulcers, conclusions are limited owing to the absence of controlled clinical trials.

Corneal transplantation activity in Catalonia, Spain, from 2011 to 2018: Evolution of indications and surgical techniques.

PURPOSE: To report corneal transplant activity carried out in Catalonia (Spain) and the evolving indications for keratoplasty over an 8-year period. METHODS: Annual reports from the Catalan Transplant Organization, Spain, on corneal graft indications and techniques from 2011 to 2018 were reviewed. RESULTS: A total of 9457 keratoplasties were performed in Catalonia, from January 2011 to December 2018. The most frequent indications were bullous keratopathy (BK; 20.5%), Fuchs endothelial dystrophy (FED; 17.9%), re-graft (13.7%), and keratoconus (11.3%). Penetrating keratoplasty (PKP) accounted for 63.4% of all performed keratoplasties. Since the introduction of eye bank precut tissue for Descemet stripping automated endothelial keratoplasty (DSAEK) in 2013 and for Descemet membrane endothelial keratoplasty (DMEK) in 2017 the number of endothelial keratoplasties has drastically increased. An increasing trend of posterior lamellar techniques over the total of keratoplasties was found (p<0.001). Endothelial keratoplasties for different endothelial diseases indications (BK, FED, and re-graft), also showed and increasing trend (p<0.001). DMEK is the technique with the highest increase (statistically significantly different from linearity) over other endothelial keratoplasties in FED (p<0.001) but not in BK (p = 0.67) or re-grafts (p = 0.067). CONCLUSION: Endothelial diseases represented the top indication for keratoplasty over the 8-year period. PKP is still the most used technique in Catalonia, but endothelial keratoplasties and especially DMEK showed a significant increasing trend over the last years. This is congruent with the main rationale nowadays for keratoplasties: to customize and transplant as less tissue as possible. Therefore, the availability of precut tissue could have definitely enforced such approach.

Systemic contribution of inflammatory mediators to the severity of diabetic and uveitic macular edema.

PURPOSE: To assess whether serum cytokine and growth factor levels are associated with diabetic macular edema (DME) and uveitic macular edema (UME) objective severity. METHODS: Cross-sectional observational study of 81 patients (1 eye/patient) with DME (n=48) and UME (n=33). Macular edema (ME) was defined upon central macular thickness (CMT) ≥ 300 µm on spectral domain optical coherence tomography (OCT). Serum samples were obtained from peripheral blood and IL-1ß, IL-6, IL-8, IL-10, MCP-1, TNF-α, and VEGF levels were determined by Luminex analysis. Main outcome measure was the correlation between mediators' levels and CMT and macular volume (MV) on OCT for ME cases. RESULTS: In DME, IL-6 levels were found to significantly correlate with MV (r=0.324; p=0.028) whereas in UME, IL-8 was significantly associated with both CMT (r=0.401; p=0.021) and MV (r=0.391; p=0.024). IL-8 independently correlated with CMT (ß=177.2; p=0.033) and MV (ß=3.17; p=0.008) in UME multivariate model. CONCLUSION: Peripheral blood IL-6 and IL-8 levels could play a role in the severity of DME and UME, respectively. IL-8 even seems to be independently associated with CMT and MV in UME cases. Such systemic implications could enforce DME and UME personalized diagnostic and therapeutic approaches.