Real-World Evidence of the Long-Term Effectiveness of 0.2 µg/Day Fluocinolone Acetonide Implant in Persistent and Recurrent Diabetic Macular Edema - A Single Center Study.

Purpose: To report the long-term functional, anatomical and safety outcomes of 0.2 µg/day fluocinolone acetonide 0.19mg in patients with persistent or recurrent diabetic macular edema (DME). Methods: Retrospective, observational, single-center study of patients with recurrent or persistent DME. All patients received 0.2 µg/day of fluocinolone acetonide 0.19mg, and data were collected at baseline and months 1, 3, 6, 12, 24 and 36 after implantation. Outcomes measured included best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), and safety outcomes. Results: A total of 28 eyes from 28 patients were included. The mean age was 66.5 years (95% CI 62.8-70.2) with a mean duration of DME of 8.8 years (95% CI 7.7-10.0). Only two eyes were phakic. Mean follow-up was 25.4 months (95% CI 21.2-29.6). Mean BCVA at baseline was 48.6 ETDRS letters (95% CI 41.3-55.8) and improved as early as month 1 of follow-up with a mean gain in BCVA of 7.8 (95% CI 4.3-11.3) ETDRS letters (p<0.001). Statistically significant improvements in BCVA were also observed at months 6, 12 and 24. At baseline, patients had a mean CMT of 530.5µm (95% CI 463.0-598.0), and a decrease in CMT was observed, starting at the first month of follow-up (mean CMT reduction of -170.5µm, 95% CI -223.8- -117.1; p<0.001). Statistically significant decreases in CMT were also observed at months 6, 12, 24, and 36, with the maximum decrease observed at month 12 (p<0.001). Mean IOP at baseline was 16.4mmHg (95% CI 15.3-17.5) and nine eyes (32.1%) had an IOP ≥21mmHg during follow-up. Conclusion: Our results support the effectiveness and safety profile of fluocinolone acetonide. Although additional long-term real-world evidence is required, fluocinolone acetonide may represent a safe strategy for daily, low-dose, sustained and localized release to the posterior segment of the eye, providing both functional and anatomical benefits in DME.

Clinical outcomes and prognostic factors in Acanthamoeba keratitis.

PURPOSE: To report clinical findings and prognostic factors for visual and morphological outcomes in patients with Acanthamoeba keratitis (AK). METHODS: Single-center, retrospective, longitudinal study of 51 cases of AK diagnosed by real-time polymerase chain reaction (RT-PCR) between March 2010 and October 2022. The primary outcome was the final best corrected visual acuity (BCVA). Poor visual outcome was defined as a final BCVA ≥ 1 logMAR unit, while good visual outcome was defined as a final BCVA < 1 logMAR unit. Eyes from these two groups were compared, regarding demographic and initial clinical variables, anti-Acanthamoeba treatment used, and complications of the disease. Early diagnosis was defined as ≤ 14 days from symptom onset to diagnostic confirmation and initiation of Acanthamoeba medical treatment. Multivariable logistic regression was used to determine predictors of poor visual outcome. RESULTS: A total of 51 eyes from 46 patients diagnosed with AK, all contact lens (CL) wearers, were included in this study. Average follow-up was 39.0 ± 30.2 [total range 14-120] months. Thirty-one eyes (60.8 %) presented good visual outcome, with a lower baseline age (30.5 ± 9.0 vs. 42.3 ± 15.8; p = 0.020), better initial BCVA (0.8 ± 0.7 logMAR units vs. 1.3 ± 0.9 logMAR units; p = 0.047), higher rate of early diagnosis (45.2 % vs. 5.6 %; p = 0.004), and higher rate of therapeutic epithelial debridement (64.5 % vs. 10 %; p < 0.001). 20 eyes (39.2 %) presented poor visual outcome, with 12 eyes undergoing evisceration/enucleation (23.5 %). These 20 eyes presented a higher rate of complications (90 % vs. 61.3 %; p = 0.031). In multivariable analysis, early diagnosis of AK (OR 19.78; 95 % CI 2.07-189.11; p = 0.010) and therapeutic epithelial debridement (OR 19.02; 95 % CI 3.27-110.57; p = 0.001) were associated with a good visual outcome. CONCLUSIONS: In the present study, poor visual outcome was present in 39 % of affected eyes. Early AK diagnosis (≤14 days from symptom onset) and therapeutic epithelial debridement were associated with good final visual outcome.

Peripapillary and Subfoveal Choroidal Thickness in Retinal Vein Occlusions.

Purpose: This work aimed to longitudinally assess the peripapillary (PPCT) and subfoveal (SFCT) choroidal thickness (CT), in patients diagnosed with central (CRVO) or branch retinal vein occlusions (BRVO), correlating SFCT with central macular thickness (CMT) and PPCT with peripapillary retinal nerve fiber layer thickness (pRNFL). Patients and Methods: This was a retrospective longitudinal study of 71 eyes from 71 patients with treatment-naïve retinal vein occlusion (24 CRVO and 40 BRVO). Spectral-domain optical coherence tomography (SD-OCT, Spectralis HRA-OCT, Heidelberg) was used to measure PPCT, SFCT, pRNFL and CMT of the affected and fellow eyes at baseline (acute phase) and at 3 and 9 months post anti-VEGF treatment. IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. A p-value ≤0.05 was considered statistically significant. Results: Affected eyes presented a thicker baseline PPCT and SFCT compared to their fellow eyes both in CRVO and BRVO (p < 0.05). Both groups presented a significant decrease of PPCT in the affected eyes at 3 months compared to baseline (p < 0.05). At 9 months, compared to 3 months, PPCT remained stable (p > 0.05). Similarly, affected eyes' SFCT significantly decreased at 3 months (p < 0.05) in both groups. At 9 months, compared to 3 months, SFCT decreased in the CRVO patients (p = 0.047) but remained stable in the BRVO patients (p = 0.850). No correIations between SFCT and CMT were seen at any timepoint in both groups (p > 0.05). PPCT correlates with pRNFL in CRVO at 3 months, although no other correlations were found during the follow-up. In BRVO, PPCT did not show any significant correlation with pRNFL. Conclusion: Both in CRVO and BRVO eyes, PPCT and SFCT at diagnosis are significantly thicker compared to the fellow eye, suggesting a possible increase in CT immediately after the occlusion, which is followed by a decrease at an early follow-up stage.

Hypotony Maculopathy Related to Anti-VEGF Intravitreal Injection.

Purpose: To describe a case of hypotony maculopathy following anti-VEGF intravitreal injection (IVI) in a patient with pseudoxanthoma elasticum (PE). Methods: Clinical case report. Results: A 52-year-old male complained of right eye (OD) vision loss 2 days after an uncomplicated anti-VEGF IVI for the treatment of choroidal neovascularization secondary to angioid streaks. Relevant medical history included PE, pathologic myopia, and a previous pars plana vitrectomy (PPV) due to a retinal detachment. OD best-corrected visual acuity (BCVA) dropped from 6/12 to 6/18 after the IVI. Intraocular pressure (IOP) was 3 mmHg and chorioretinal folds were evident in the posterior pole. Topical dexamethasone and atropine were prescribed, and full recovery was noticed after 3 days. Four months later, the patient developed a new episode of vision loss after another IVI. His BCVA was counting fingers, IOP was 2mmHg, and more noticeable chorioretinal folds were found. This time, an open scleral wound at the injection site was evident and a scleral suture was necessary. Once again, the patient recovered well. Conclusion: Hypotony maculopathy following intravitreal injection is a rare condition. However, the described patient presented several conditions which could be related with poor scleral wound closure: intrinsic scleral fragility due to myopia and pseudoxanthoma elasticum; repeated IVI procedures; and absence of vitreous in the posterior segment due to prior vitrectomy. Despite the good outcome, hypotony maculopathy may be a sight-threatening condition, and special attention is necessary for specific patients with risk factors.

A drug discovery approach based on comparative transcriptomics between two toxin-secreting marine annelids: Glycera alba and Hediste diversicolor.

Most animal toxins evolved to interact with specific molecular targets, which makes them highly-prized bioactives for drug development. Marine toxins, in particular, due to their wide chemical diversity, offer a new range of possibilities, a few of which have already been translated into approved drugs. Glycera alba and Hediste diversicolor are sympatric Polychaeta with distinct ecology and behavior suspected to secrete toxins that evolved to interact with distinct molecular targets, thus with differential selectivity and potential applications in drug discovery. Comparative transcriptomics revealed that while G. alba's venom apparatus is localized in the proboscis and neurotoxins are secreted to overtake prey, H. diversicolor secretes fewer and less specific toxins that are seemingly a defense. Human interactome-directed analysis unraveled novel toxins and other bioactives with potential biomedical applications, like proteins from G. alba's venom that can regulate apoptosis, whereas H. diversicolor yielded proteins that may control inflammation and cell proliferation in humans. Omics and bioinformatics appear to be powerful tools for marine bioprospecting and drug discovery, enabling molecular mining through transcriptomes of non-model organisms and link their ecology and physiology with protein's specificity and bioreactivity. Interactome-directed analysis against the human proteome seems an efficient alternative to the design of synthetic drugs.

Bilateral Episcleral Corkscrew Vessels: Expedition into the Unknown - Case Report.

We aim to report a case of a middle-aged woman with bilateral idiopathic elevated episcleral venous pressure (IEEVP) and its difficulties in the diagnostic approach. Particularly in this case, the atypical feature of ocular hypertension without glaucomatous optic nerve damage may be misleading. We present a 66-year-old woman with longstanding bilateral "red eyes." Clinical findings included bilateral episcleral vessel engorgement and tortuosity and raised intraocular pressure with open iridocorneal angles. Despite ocular hypertension, glaucomatous neuropathy was absent and confirmed by normal structural (optical coherence tomography) and functional (standard automated perimetry) tests. The systemic workup was unremarkable. Magnetic resonance angiography showed bilateral dilated superior ophthalmic veins. Cerebral digital subtraction angiography was requested, and no carotid-cavernous fistula (or other significant vascular findings) was identified. The diagnosis of IEEVP was assumed. In conclusion, our case highlights the systematic investigation necessary in cases of bilateral episcleral vessel engorgement and tortuosity and the possible differential diagnosis to be considered to rule out life-threatening causes of elevated episcleral venous pressure. It is important for clinicians to be aware of IEEVP even in patients with atypical features that despite significative ocular hypertension had no glaucomatous damage.

Does Predation Exacerbate the Risk of Endosymbiont Loss in Heat Stressed Hermatypic Corals? Molecular Cues Provide Insights Into Species-Specific Health Outcomes in a Multi-Stressor Ocean.

Ocean warming has been a major driver of coral reef bleaching and mass mortality. Coupled to other biotic pressures, corals' ability for acclimatization and adaptation may become compromised. Here, we tested the combined effects of warming scenarios (26, 30, and 32°C) and predation (wound vs. no wound) in coral health condition (paleness, bleaching, and mortality), cellular stress responses (heat shock protein 70 kDa Hsp70, total ubiquitin Ub, and total antioxidant capacity TAC), and physiological state (integrated biomarker response index, IBR) of seven Scleractinian coral species, after being exposed for 60 days. Results show that although temperature was the main factor driving coral health condition, thermotolerant species (Galaxea fascicularis, Psammocora contigua, and Turbinaria reniformis) displayed increased paleness, bleaching, and mortality in predation treatments at high temperature, whereas thermosensitive species (Acropora tenuis, Echinopora lamellosa, and Montipora capricornis brown and green morphotypes) all died at 32°C, regardless of predation condition. At the molecular level, results show that there were significant main and interactive effects of species, temperature, and predation in the biomarkers assessed. Temperature affected Hsp70, Ub, and TAC, evidencing the role of protein folding and turnover, as well as reactive oxygen species scavenging in heat stress management. Predation increased Hsp70 and Ub, suggesting the activation of the pro-phenoloxidase system and cytokine activity, whereas the combination of both stressors mainly affected TAC during moderate stress and Ub under severe stress, suggesting that redox balance and defense of homeostasis are crucial in tissue repair at high temperature. IBR levels showed an increasing trend at 32°C in predated coral fragments (although non-significant). We conclude that coral responses to the combination of high temperature and predation pressure display high inter-species variability, but these stressors may pose a higher risk of endosymbiont loss, depending on species physiology and stress intensity.

Correlation Between Ophthalmologic and Neuroradiologic Findings in Type 1 Neurofibromatosis.

BACKGROUND: Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings. METHODS: This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established. RESULTS: Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings. CONCLUSIONS: This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients.

Scleral Fixation of Akreos AO60 Intraocular Lens Using Gore-Tex Suture: An Eye on Visual Outcomes and Postoperative Complications.

PURPOSE: "In-the-bag" placement of an IOL is the Holy Grail for any cataract surgeon. However, in the absence of capsular integrity, alternative surgical options to place the IOL must be sought. We aim to report the clinical outcomes and safety profile of scleral-fixated Akreos AO60 intraocular lens implantation using Gore-Tex suture, combined with pars plana vitrectomy. METHODS: This is a single-center, retrospective case series descriptive study. Electronic clinical records of all patients subjected to scleral fixation of a Bausch and Lomb Akreos AO60 IOL combined with pars plana vitrectomy, between April 1, 2017, and August 1, 2021, were reviewed. Data concerning age, sex, laterality, past ophthalmological history, pre- and postoperative best-available visual acuity, surgical indication, and intra- and postoperative complications were collected. Measured outcomes were the differences in best-available visual acuity and frequency of postoperative complications. RESULTS: A total of 37 eyes (20 right eyes and 17 left eyes) from 36 patients (16 females and 20 males) were included in the statistical analysis. The mean age at time of surgery was 72.0 ± 12.4 years. The mean follow-up period was 548.9 days (range 39-1564 days). Globally, the mean best-available logMAR visual acuity improved from 1.61 preoperatively (0.025 decimal equivalent) to 0.57 postoperatively (0.3 decimal equivalent), this difference being statistically significant (P < 0.001). Indications for surgery included aphakia due to complicated cataract surgery (24.3%; n = 9); subluxated IOL due to closed trauma (21.6%; n = 8); PEX-related subluxated IOL (16.2%; n = 6); non-traumatic, non-PEX-related subluxated IOL (18.9%; n = 7); subluxated crystalline lens due to closed trauma (8.1%; n = 3); aphakia due to open-globe injury (5.4%; n = 2); silicone-induced IOL opacification (2.7%; n = 1); and aphakia post-endophthalmitis (2.7%; n = 1). Postoperative complications included transient ocular hypertension (27.0%; n = 10), transient corneal edema (18.9%; n = 7), cystoid macular edema (18.9%, n = 7), self-limited hypotension (5.4%, n = 2), self-limited vitreous hemorrhage (2.7%, n = 1), central retinal vein occlusion (2.7%, n = 1), late retinal detachment (2.7%, n = 1), and Akreos IOL opacification (2.7%, n = 1). No suture-related complications were observed. CONCLUSION: There was a statistically significant improvement in visual acuity after scleral fixation of Akreos AO60 intraocular lens using Gore-Tex suture, with no suture-related problems recorded. This procedure seems to be a valuable alternative for posterior chamber IOL placement when secondary IOL implantation is required.

Two Novel Disease-Causing Variants in the PDE6C Gene Underlying Achromatopsia.

We report the clinical phenotype and genetic findings of two variants in PDE6C underlying achromatopsia (ACHM). Four patients with the variant c.1670G>A in exon 13 of the PDE6C gene were identified. Additionally, one had compound heterozygous genotype, with two variants in the PDE6C gene, a variant of c.2192G>A in exon 18 and c.1670G>A in exon 13. All patients presented the symptomatic triad of decreased visual acuity, severe photophobia, and colour vision disturbances. SD-OCT showed an absence of the ellipsoid zone, creating an optically empty cavity at the fovea in three patients. The patient with the compound heterozygous genotype presented a more severe subfoveal outer retina atrophy. ERG recordings showed extinguished responses under photopic and 30-Hz flicker stimulation, with a normal rod response. We identified two new variants in the PDE6C gene that leads to ACHM.

Proteomics in systems toxicology.

Proteins are the ultimate product of gene expression. As they hinge between gene transcription and phenotype, they offer a more realistic perspective of toxicopathic effects, responses and even susceptibility to insult than targeting genes and mRNAs while dodging some inter-individual variability that hinders measuring downstream endpoints like metabolites or enzyme activity. Toxicologists have long focused on proteins as biomarkers but the advent of proteomics shifted risk assessment from narrow single-endpoint analyses to whole-proteome screening, enabling deriving protein-centric adverse outcome pathways (AOPs), which are pivotal for the derivation of Systems Biology informally named Systems Toxicology. Especially if coupled pathology, the identification of molecular initiating events (MIEs) and AOPs allow predictive modeling of toxicological pathways, which now stands as the frontier for the next generation of toxicologists. Advances in mass spectrometry, bioinformatics, protein databases and top-down proteomics create new opportunities for mechanistic and effects-oriented research in all fields, from ecotoxicology to pharmacotoxicology.

Long-term progression of geographic atrophy in age-related macular degeneration does the phakic status matter?

PURPOSE: To assess the long-term risk of geographic atrophy (GA) progression after cataract surgery. METHODS: Subjects with GA secondary to AMD followed for at least 1 year with fundus autofluorescence imaging and with at least two visits at our centre were included. Patients with wet AMD, disciform scar, past history of intravitreal injections or laser treatment, other maculopathies and with poor quality images were excluded. GA area at baseline and at follow-up visit was measured. Three study groups were defined according to their phakic status: (A) pseudophakia, (B) phakic and (C) phacoemulsification surgery performed during the study. Differences of GA area progression were compared between these study groups. In addition, comparison between GA progression rate in group (C) before and after the surgery was performed. The enlargement rate (ER) was calculated for lesion size after transforming the measurements to the square-root scale. RESULTS: A total of 92 eyes of 92 patients were enrolled. Median follow-up time was 4 [1-10] years. Regarding the eye's phakic status, 29 (31.5%) were pseudophakic and 63 (68.5%) were phakic; of these, 22 underwent phacoemulsification during the study. Overall, the median baseline and follow-up area of GA were 1.42 [0.04-32.10] mm2 and 6.48 [0.25-47.40] mm2, respectively. The ER was similar between phakic and pseudophakic eyes (0.18 [0.01-1.03] vs 0.15 [0.01-0.65] mm/year, p = 0.62). In patients that underwent cataract surgery during the study, the GA ER remained stable (0.13 [0.01-0.92] vs 0.14 [0.01-0.63] mm/year, p = 0.43). CONCLUSION: These results suggest that cataract surgery does not increase the risk of pre-existing GA progression. Therefore, cataract surgery seems safe and a potential therapeutic weapon to improve visual acuity and consequently quality of life in GA patients.

Anterior Chamber Versus Ciliary Sulcus Ahmed Glaucoma Valve Tube Placement: Longitudinal Evaluation of Corneal Endothelial Cell Profiles.

PRCIS: An Ahmed glaucoma valve (AGV) tube in the ciliary sulcus (CS) is safer for the endothelium. At 4 years of follow-up, there was a significant decrease in endothelial cell count only with anterior chamber (AC) placement. PURPOSE: Corneal endothelium (CE) damage is one of the most feared long-term complications that can result from glaucoma drainage devices. Nonetheless, there is a lack of studies evaluating longitudinal changes in CE cells. This study aims to compare CE changes after AGV implantation in eyes with AC or CS tube placement. MATERIALS AND METHODS: This was a retrospective, nonrandomized, longitudinal study of pseudophakic eyes with open-angle glaucoma and medically uncontrolled intraocular pressure that received an AGV. Eyes with additional glaucoma surgeries performed during follow-up were excluded. The main outcome measure was endothelial cell density (ECD), which was evaluated 1 year±2 months and 4 years±2 months postoperatively. The average endothelial cell size (AS) and the distance from the tube tip to the cornea were also evaluated. RESULTS: Twenty-six eyes from 26 patients, with a mean age of 73±10 years, were included. The tube was placed in the AC in 15 eyes and in the CS in 11 eyes. The eyes with tube placement in the AC showed a significant AS increase (P=0.007) and ECD decrease (P=0.034), whereas eyes with tube placement in the CS had no significant AS (P=0.575) or ECD (P=0.445) change. In the eyes with tube placement in the AC, there was no correlation between DTC and ECD (P=0.260) or AS (P=0.428) changes. CONCLUSIONS: Tube placement in the AC seems to lead to significant CE cell loss over time, compared with tube placement in the CS.

Conserved fatty acid profiles and lipid metabolic pathways in a tropical reef fish exposed to ocean warming - An adaptation mechanism of tolerant species?

Climate warming is causing rapid spatial expansion of ocean warm pools from equatorial latitudes towards the subtropics. Sedentary coral reef inhabitants in affected areas will thus be trapped in high temperature regimes, which may become the "new normal". In this study, we used clownfish Amphiprion ocellaris as model organism to study reef fish mechanisms of thermal adaptation and determine how high temperature affects multiple lipid aspects that influence physiology and thermal tolerance. We exposed juvenile fish to two different experimental conditions, implemented over 28 days: average tropical water temperatures (26 °C, control) or average warm pool temperatures (30 °C). We then performed several analyses on fish muscle and liver tissues: i) total lipid content (%), ii) lipid peroxides, iii) fatty acid profiles, iv) lipid metabolic pathways, and v) weight as body condition metric. Results showed that lipid storage capacity in A. ocellaris was not affected by elevated temperature, even in the presence of lipid peroxides in both tissues assessed. Additionally, fatty acid profiles were unresponsive to elevated temperature, and lipid metabolic networks were consequently well conserved. Consistent with these results, we did not observe changes in fish weight at elevated temperature. There were, however, differences in fatty acid profiles between tissue types and over time. Liver showed enhanced α-linolenic and linoleic acid metabolism, which is an important pathway in stress response signaling and modulation on environmental changes. Temporal oscillations in fatty acid profiles are most likely related to intrinsic factors such as growth, which leads to the mobilization of energetic reserves between different tissues throughout time according to organism needs. Based on these results, we propose that the stability of fatty acid profiles and lipid metabolic pathways may be an important thermal adaptation feature of fish exposed to warming environments.

Predicting retinal pigment epithelium remodelling and its functional impact.

PURPOSE: To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes. METHODS: Retrospective longitudinal study of patients with retinal pigment epithelium (RPE) tears secondary to age-related macular degeneration (AMD). Imaging was performed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). RPE layer integrity in the RPE-denuded area was examined with SD-OCT, and variation in the RPE-denuded homogeneous hypofluorescent area was examined with FAF over time for each case (eye). Patients were divided in two groups, according to the presence (Rem) or absence (No Rem) of evidence of RPE tear remodelling. Data were collected at three different time points: at baseline (at diagnosis of exudative AMD), at RPE tear diagnosis, and at the last available follow-up. Using SD-OCT, the following parameters were evaluated: type of CNV, type of PED and its dimensions, presence of subretinal (SRF) or intraretinal (IRF) fluid, central retinal thickness (CRT), presence and location of hyperreflective dots, and dimension and location of RPE tear. RESULTS: This study included 32 eyes from 31 patients (19 female and 12 male), with RPE tears secondary to AMD. RPE remodelling after tear development was evident in 17 (53.1%) eyes after 7 [1-59] months. Anatomical recovery was associated with a younger age at RPE tear diagnosis (73 ± 7 vs. 81 ± 7 years old, p=0.01), smaller and narrower retinal pigment epithelial detachment (PED) at tear diagnosis (height 369 vs. 602 µm, p=0.02; width 2379 vs. 3378 µm, p=0.04), and the presence of SRF at tear diagnosis (94% vs. 53%, p=0.02). After adjusting for other covariates, a younger age at RPE tear diagnosis maintained significant association with RPE tear remodelling. RPE tear remodelling did not correlate with a better visual outcome at last follow-up (43 ± 22.8 vs. 34 ± 23.8 ETDRS letters, p=0.30). Final VA was directly proportional to VA at tear diagnosis (r= 0.654; p<0.001) and correlated negatively with PED width at tear diagnosis (r = -0.388; p=0.03). CONCLUSION: RPE remodelling was evident in half of our sample and was associated with a younger age, smaller and narrower PED at RPE tear diagnosis, and presence of SRF also at tear diagnosis. Nevertheless, this structural recovery did not result in a better functional outcome.

Covid-19 Impact on Macular Neovascularization and Retinal Vein Occlusion Treatment: Single-Center Experience.

PURPOSE: The aim of this study was to evaluate whether the coronavirus disease 19 (COVID-19) pandemic resulted in undertreatment and subsequent loss of visual acuity (VA) in patients with macular neovascularization (MNV) or retinal vein occlusion (RVO) regularly treated with intravitreal antivascular endothelial growth factor injections. METHODS: Single-center, retrospective study of patients scheduled for treatment between March 19 and June 1, 2020, the national mandatory quarantine period. Patients' demographics, VA, and scheduled treatment during this period were reviewed via medical records. All patients were analyzed regarding treatment attendance rates. The visual impact of COVID-19 was assessed in patients who had been treated and presented a stable VA for >6 months before the beginning of the quarantine. RESULTS: This study included 927 eyes from 769 patients. The attendance rate increased throughout the study timeframe (p < 0.001) and correlated negatively with higher patient's age (r = -0.142; p = 0.005). Patients with age-related macular degeneration (67.6%) had lower attendance rates (p = 0.007) and were older (p < 0.001). The visual impact analysis included 400 eyes from 325 patients. The average VA variation throughout this period was -1.7 ± 8.4 ETDRS letters and was similar in different retinal pathologies (p = 0.334). VA variation did not correlate with the number of missed treatments per patient (r = 0.100; p = 0.150). The prevalence of subretinal fluid and intraretinal fluid, as well as central retinal thickness decreased significantly throughout the study period (p values of <0.001, <0.001, and 0.032, respectively). CONCLUSION: The COVID-19 pandemic had a significant impact on the attendance rate of patients with MNV or RVO to their scheduled treatments, which was higher in the first week of mandatory quarantine. Nevertheless, VA did not decrease significantly during this period, with a limited VA variation regardless of primary retinal disorder and morphological parameters even improved in the eyes included in the visual impact analysis.

Longitudinal Retinal Changes Induced by Hydroxychloroquine in Eyes without Retinal Toxicity.

INTRODUCTION: This study aimed to evaluate the longitudinal changes in retinal layer thickness in patients treated with hydroxychloroquine without retinal toxicity. METHODS: This is a longitudinal retrospective study of patients taking hydroxychloroquine followed in a hydroxychloroquine retinal toxicity screening program of a tertiary hospital between January 2010 and April 2019. Patients who performed 2 optical coherence tomography (OCT) scans at least 1 year apart were included. All subjects with hydroxychloroquine suspected or confirmed retinal toxicity, glaucoma, retinal pathology, or poor segmented images were excluded. Spectral-domain optical coherence tomography (Spectralis HRA-OCT, Heidelberg) was used to evaluate the macular area. Automatically segmented ETDRS retinal thickness maps were compared between the first and the last OCT evaluation available. Full retina (FR), inner retina (IRL), ganglion cells (GCL), inner nuclear (INL), and outer retina (ORL) layer thicknesses were measured in the foveolar, paracentral, and peripheral area. RESULTS: The population included 144 eyes of 144 patients. The mean interval between OCT scans was 38.1 ± 18.4 months, and the mean cumulative dose was 406.9 ± 223.9 g. Foveolar (p = 0.040, p = 0.006, and p = 0.001, respectively) and paracentral (p = 0.006, p = 0.001, and p = 0.005, respectively) FR, IRL, and GCL decreased overtime. No differences were found in INL or ORL. A very weak correlation was found between age and foveal IRL change overtime (p = 0.037; R = 0.175), as well as between the hydroxychloroquine time of use and foveal GCL variation (p = 0.032; R = 0.179). CONCLUSION: Hydroxychloroquine was found to cause progressive thinning of the inner retinal layers, specifically in the GCL of the foveolar and paracentral areas, but no changes were observed in the outer retina.

Different sensitivity to heatwaves across the life cycle of fish reflects phenotypic adaptation to environmental niche.

Predicting responses of marine organisms to global change requires eco-physiological assessments across the complex life cycles of species. Here, we experimentally tested the vulnerability of a demersal temperate fish (Sparus aurata) to long-lasting heatwaves, on larval, juvenile and adult life-stages. Fish were exposed to simulated coastal (18 °C), estuarine (24 °C) summer temperatures, and heatwave conditions (30 °C) and their physiological responses were assessed based on cellular stress response biomarkers (heat shock protein 70 kDa, ubiquitin, antioxidant enzymes, lipid peroxidation) and phenotypic measures (histopathology, condition and mortality). Life-stage vulnerability can be ranked as larvae > adults > juveniles, based on mortality, tissue pathology and the capacity to employ cellular stress responses, reflecting the different environmental niches of each life stage. While larvae lacked acclimation capacity, which resulted in damage to tissues and elevated mortality, juveniles coped well with elevated temperature. The rapid induction of cytoprotective proteins maintained the integrity of vital organs in juveniles, suggesting adaptive phenotypic plasticity in coastal and estuarine waters. Adults displayed lower plasticity to heatwaves as they transition to deeper habitats for maturation, showing tissue damage in brain, liver and muscle. Life cycle closure of sea breams in coastal habitats will therefore be determined by larval and adult stages.