BASELINE SATTLER LAYER-CHORIOCAPILLARIS COMPLEX THICKNESS CUTOFFS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION PROGRESSION.

PURPOSE: To assess the relationship between choroidal overall and sublayer thickness and age-related macular degeneration (AMD) stage progression. METHODS: A prospective, observational case series was performed. Two hundred and sixty-two eyes of 262 patients with different stages of AMD were imaged by optical coherence tomography. Age-related macular degeneration stage, choroidal thickness, Sattler layer-choriocapillaris complex thickness (SLCCT), and Haller layer thickness were determined at the baseline visit, at a 1-year follow-up visit, at a 2-year follow up visit, and at a final visit (performed after a mean of 5 ± 1 year from the baseline visit). RESULTS: Baseline AMD stages were distributed as follows: early AMD (30 eyes; 12%), intermediate AMD (97 eyes; 39%), and late AMD (126 eyes; 49%). At the final follow-up, AMD stages were so distributed: early AMD (14 eyes; 6%), intermediate AMD (83 eyes; 33%), and late AMD (156 eyes; 61%). Each group showed a statistically significant decrease in choroidal thickness values over the entire follow-up ( P < 0.001), and SLCCT reduction was associated with AMD progression ( P < 0.001). Moreover, SLCCT quantitative cutoffs of <20.50 µ m and <10.5 µ m were associated with a moderate and high probability of AMD progression, respectively, and SLCCT quantitative cutoffs of <18.50 µ m and <8.50 µ m implied a moderate and high probability of macular neovascularization onset, respectively. CONCLUSION: Progressive choroidal impairment contributes to AMD progression. Among choroidal layers, a reduced SLCCT is a promising biomarker of disease worsening, and its quantitative evaluation could help to identify patients at higher risk of stage advancement.

Extended depth-of-focus (EDOF) AcrySof® IQ Vivity® intraocular lens implant: a real-life experience.

PURPOSE: Extended depth-of-focus (EDOF) is a promising intraocular lens (IOL) technology for cataract surgery. The aim of the study was to report the real-life experience related to the implant of EDOF AcrySof® IQ Vivity® (Alcon Inc., USA) IOL. METHODS: The study was designed as a interventional, prospective, case series with 3 months of follow-up. Patients needing cataract surgery, without any other kind of ocular diseases, were recruited and implanted with AcrySof® IQ Vivity® IOL. We evaluated the refractive success of this IOL through complete ophthalmologic assessments and the administration of the Quality of Vision test. The main outcome measures were the refractive outcome; far, intermediate, and near vision; and Quality of Vision score. RESULTS: We included 108 eyes (54 patients; age 62 ± 5 years). Intra-operative and post-operative complications were 0%. Thirty out of 100 eyes (28%) required toric IOL. Best-corrected visual acuity improved from 0.4 ± 0.3 LogMAR to 0.0 ± 0.0 LogMAR (p < 0.01). Refractive outcome was very good for far and intermediate visions, whereas a spherical addition of at least + 1.0D was required for near vision. The mean Quality of Vision score was of 15.5 ± 6.5. The most complained visual disturbances were haloes and glares, although resulting well-tolerated. Dynamic pupillometry findings well-correlated with the amount of complained post-operative visual discomforts. CONCLUSIONS: AcrySof® IQ Vivity® IOL is a well-tolerated choice to correct far and intermediate vision. Spectacles are needed to optimize near vision. Our data strongly suggest dynamic pupillometry as a useful investigation to optimize post-operative refractive success.

QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY PARAMETER VARIATIONS AFTER TREATMENT OF MACULAR NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Macular neovascularization (MNV) secondary to age-related macular degeneration can be characterized by quantitative optical coherence tomography angiography. The aim of the study was to assess the evolution of quantitative optical coherence tomography angiography parameters after 1 year of antivascular endothelial growth factor injections. METHODS: Naive age-related macular degeneration-related MNV eyes were prospectively recruited to analyze optical coherence tomography and optical coherence tomography angiography parameters, including MNV vessel tortuosity (VT) and reflectivity, at baseline and at the end of the follow-up. Macular neovascularization eyes were categorized by a MNV VT cutoff, and quantitative parameter variations were documented after 1 year of treatment. We divided MNV eyes into Group 1 (MNV VT < 8.40) and Group 2 (MNV VT > 8.40). RESULTS: Thrity naive age-related macular degeneration-related MNV eyes (30 patients) were included. Our cohort included 18 Type 1 MNV and 12 Type 2 MNV lesions. Baseline central macular thickness (411 ± 85 µm) improved to 323 ± 54 µm at 1 year (P < 0.01). Only Group 1 MNV displayed significant visual improvement. Macular neovascularization VT values remained stable over the follow-up in both subgroups. Group 2 MNV eyes showed increased MNV reflectivity and increased MNV area at the end of the follow-up. Quantitative retinal capillary plexa parameters were found to be worse in Group 2 MNV. Outer retinal atrophy occurred in 2 of the 18 eyes in MNV Group 1 (11%) and in 6 of the 12 eyes in MNV Group 2 (50%) after 1 year. Vessel density proved to be always worse in Group 2 than in Group 1. CONCLUSION: Macular neovascularization VT provides information on the blood flow and identifies two subgroups with different final anatomical and visual outcomes, regardless of the treatment effect.

Extrafoveal Müller cells detection in vivo in the human retina: A pilot study based on optical coherence tomography.

Müller cells (MC) represent a key element for the metabolic and functional regulation of the vertebrate retina. The aim of the present study was to test the feasibility of a new method for the in-vivo detection and quantification of extrafoveal MC in human retina. We developed a new approach to isolate and analyse extrafoveal MC in vivo, starting from structural optical coherence tomography data. Our pilot investigation was based on the optical properties of MC, which are known to not interfere with the light reaching the outer retinal structures. We reconstructed MC in the macular region of 18 healthy subjects and the quantitative analyses revealed ~42,000/9 mm2 cells detected. Furthermore, we included 2 patients affected by peripheral intraocular melanoma, with macular sparing, needing surgical enucleation. We used these two eyes to perform a qualitative comparison between our reconstructions and histological findings. Our study represents the first pilot investigation dedicated on the non-invasive isolation and quantification of MC, in-vivo, in human retina. Although we are aware that our study has several limitations, first of all related with the proper detection of foveal MC, because of the peculiar z-shape morphology, this approach may open new opportunities for the non-invasive in vivo analysis of MC, providing also potential useful perspectives in retinal diseases.

HYPERREFLECTIVE FOVEAL SPOTS IN PATIENTS WITH VITREORETINAL ANOMALIES: A Qualitative and Quantitative Analysis.

PURPOSE: To describe structural optical coherence tomography (OCT) and OCT angiography features in patients who have developed hyperreflective foveal spots with or without vitreomacular interface abnormalities or with vitreous adhesion alone. METHODS: The study design was observational and cross sectional. The presence of defined epiretinal membrane was considered an exclusion criterion. All patients underwent complete ophthalmologic examination, with structural OCT and OCT angiography acquisitions. Both qualitative and quantitative analyses of OCT angiography reconstructions were performed for superficial capillary plexus, deep capillary plexus, and choriocapillaris. RESULTS: Thirty patients (20 men; mean age, 55.2 years) showing hyperreflective foveal spots on structural OCT and 30 healthy control subjects (20 men; mean age, 54.7 years) were enrolled. Best-corrected visual acuity was 0.0 ± 0.0 logarithm of the minimum angle of resolution (20/20 Snellen) for both patients and control subjects. Following global and parafoveal/extrafoveal analyses, both superficial capillary plexus and deep capillary plexus showed significant reduction (P < 0.001). Significant superficial capillary plexus and deep capillary plexus changes were also detected in contralateral eyes (P < 0.001). CONCLUSION: Hyperreflective foveal spots might be seen as the initial effect of traction forces causing Müller cell and external retinal layer disruption, leading to the onset of vitreomacular disease. These changes also have an effect on the retinal vascular network. Further larger prospective studies are necessary to confirm our findings.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CAN CATEGORIZE DIFFERENT SUBGROUPS OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Choroidal neovascularization (CNV) is a common complication of patients affected by age-related macular degeneration, showing a highly variable visual outcome. The main aim of the study was, at baseline, to perform a quantitative optical coherence tomography angiography assessment of CNV secondary to age-related macular degeneration and to assess posttreatment outcomes. METHODS: Seventy-eight naïve age-related macular degeneration-related CNV patients (39 men, mean age 78 ± 8 years) were recruited and underwent complete ophthalmologic evaluation and multimodal imaging. Several OCT and optical coherence tomography angiography parameters were collected, including vessel tortuosity and vessel dispersion (VDisp), measured for each segmented CNV. All patients underwent anti-vascular endothelial growth factor PRN treatment. Vessel tortuosity and VDisp values of CNVs were tested at baseline to establish a cutoff able to distinguish clinically different patient subgroups. RESULTS: Mean best-corrected visual acuity was 0.49 ± 0.57 (20/62) at baseline, improving to 0.31 ± 0.29 (20/41) at the 1-year follow-up (P < 0.01), with a mean number of 6.4 ± 1.9 injections. Our cohort included the following CNV types: occult (45 eyes; 58%), classic (14 eyes; 18%), and mixed (19 eyes; 24%). Observing optical coherence tomography angiography parameters, classic, mixed, and occult CNV revealed significantly different values of VDisp, with classic forms showing the highest values and the occult CNVs showing the lowest (P < 0.01); mixed forms displayed intermediate VDisp values. The ROC analysis revealed that a CNV vessel tortuosity cut-off of 8.40, calculated at baseline, enabled two patient subgroups differing significantly in visual outcomes after anti-vascular endothelial growth factor treatment to be distinguished. CONCLUSION: A baseline quantitative optical coherence tomography angiography-based parameter could provide information regarding both clinical and functional outcomes after anti-vascular endothelial growth factor treatment in age-related macular degeneration-related CNV.

OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM.

PURPOSE: To study multimodal imaging features of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). METHODS: Six patients (3 males, mean age 11 years) and a healthy age-matched control group made up of 15 healthy subjects (8 males, mean age 12.6 years) were included in the analysis. Complete ophthalmologic examination was performed, including best-corrected visual acuity, anterior and posterior segment slit-lamp evaluation, and tonometry. The multimodal imaging protocol included fundus images, structural optical coherence tomography (OCT), and swept-source OCT angiography (OCTA). The main outcome measures included the qualitative evaluation of both OCT and OCTA features of CHRRPE, retinal and choroidal thickness measurements, and the quantitative analysis of superficial capillary plexus, deep capillary plexus, and choriocapillaris vessel densities. RESULTS: Optical coherence tomography features of CHRRPE were examined extensively. Multiple little hyperreflective triangular outer retinal alterations were found at the CHRRPE edges in all patients; these were dubbed the "shark-teeth" sign. Optical coherence tomography angiography showed rarefaction and morphologic alterations of all retinal plexa. Moreover, quantitative analysis revealed a statistically significant decrease in superficial capillary plexus, deep capillary plexus, and choriocapillaris vessel densities in patients affected by CHRRPE compared with the control group. CONCLUSION: Optical coherence tomography and OCTA analyses allowed the accurate qualitative and quantitative analyses of CHRRPE features. Further studies are needed to better define OCTA changes of CHRRPE better and to improve our understanding of the possible causes of the shark-teeth sign.

VASCULAR ALTERATIONS REVEALED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH CHOROIDEREMIA.

PURPOSE: Choroideremia is a rare degenerative retinal disease that causes incurable blindness. It occurs as a result of the deficiency of the X-linked CHM gene, which encodes the Rab escort protein 1 (REP1). Gene therapy has been developed to treat CHM using adeno-associated viral vectors and is currently undergoing clinical trials. Expression of the CHM gene is ubiquitous throughout the retina, and it is therefore important to identify which retinal layers are affected in the disease process. The purpose of this study was to assess in particular the choriocapillaris using optical coherence tomography angiography because this layer is difficult to see with conventional imaging techniques. METHODS: Six men with choroideremia were identified and underwent standardized optical coherence tomography angiography as part of an ethics-approved clinical study and were compared with age-matched control subjects. RESULTS: The choriocapillaris appeared normal in regions where the retinal pigment epithelium remained intact, but it was deficient elsewhere. The outer retinal vasculature showed significant changes peripherally but also some changes centrally. The inner retinal vasculature appeared unaffected by the disease process. CONCLUSION: Choroideremia is a disease in which the choriocapillaris maintains a normal structure until the loss of the overlying retinal pigment epithelium. The inner retina also appears not to be affected at the vascular level. Although this study is limited by the small number of patients eligible for inclusion in the study, the observations support the concept of targeting gene therapy to the retinal pigment epithelium and outer retina because there is no evidence of independent degeneration of the choriocapillaris.

Microvascular Retinal and Choroidal Changes in Retinal Vein Occlusion Analyzed by Two Different Optical Coherence Tomography Angiography Devices.

PURPOSE: To investigate retinal and choroidal microvascular changes and structural choroidal involvement in retinal vein occlusion (RVO). METHODS: Retrospective analysis of treatment-naïve macular edema secondary to RVO, studied by optical coherence tomography (OCT) and OCT angiography (OCTA), before and after the loading phase of intravitreal injections of ranibizumab (IVR-LP). OCTA was performed using two different devices: AngioVue RTVue XR Avanti (spectral-domain OCTA) and Zeiss PLEX® Elite 9000 (swept-source OCTA). RESULTS: 30 eyes of 30 consecutive patients (17 branch and 13 central RVO) were included. Central macular thickness and subfoveal choroidal thickness (SCT) were significantly reduced after IVR-LP (p < 0.001 and p = 0.046, respectively). 23 eyes were eligible for OCTA analysis. Baseline vessel density (VD) in deep capillary plexus (DCP) was significantly reduced in RVO eyes compared with fellow eyes (p = 0.03 and p = 0.002 for PLEX® Elite and AngioVue, respectively). After IVR-LP, no significant VD changes in any vascular layer was found. PLEX® Elite VD analysis showed significant differences in DCP between ischemic versus non-is-chemic eyes (p = 0.011). CONCLUSION: OCTA suggests a retinal vascular impairment of DCP but no involvement of choroid in RVO eyes. A greater baseline SCT could be due to a choroidal exudation. OCTA imaged with PLEX® Elite allowed to differentiate ischemic and non-ischemic patients at baseline.

Quantitative Multimodal Imaging Characterization of Intraretinal Cysts versus Degenerative Pseudocysts in Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To differentiate intraretinal fluid (IRF) cysts from degenerative pseudocysts in neovascular age-related macular degeneration (AMD) by quantitative multimodal imaging. DESIGN: Observational, cross-sectional. PARTICIPANTS: Patients affected by macular neovascularization secondary to AMD. METHODS: All patients were analyzed by OCT, OCT angiography (OCTA), and dense automatic real-time (ART) OCTA. New-onset cysts were considered IRF, whereas those cysts that were found to be persistent for at least 3 months were categorized as degenerative pseudocysts. Intraretinal cysts were automatically segmented to calculate cyst circularity. Peri-cyst space was quantitatively analyzed to assess the presence of perfusion signal and hyperreflective foci (HF). MAIN OUTCOME MEASURES: Best-corrected visual acuity, cyst circularity, peri-cyst perfusion, peri-cyst HF, fibrosis, and outer retinal atrophy. RESULTS: We analyzed 387 cysts collected from 35 eyes of 35 patients with neovascular AMD (14 men; mean age, 80 ± 5 years). We classified 302 IRF cysts and 85 degenerative pseudocysts. Intraretinal fluid cysts were characterized by significantly higher circularity (0.86; range, 0.81-0.91), perfusion signal in the peri-cyst space, and peri-cyst HF in 89% of cases (all P < 0.05). Degenerative pseudocysts showed significantly lower circularity (0.68; range, 0.64-0.76), no perfusion signal in the peri-cyst space, and peri-cyst HF in only 29% of cases (all P < 0.05). The adopted quantitative metrics significantly correlated with disease duration, number of injections, fibrosis, and outer retinal atrophy. CONCLUSIONS: Intraretinal fluid cysts can be discriminated from degenerative pseudocysts using a quantitative multimodal imaging approach. These findings are clinically relevant and should be included in future training models for artificial intelligence algorithms to improve the diagnostic power and fluid monitoring in neovascular AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ophthalmologists' awareness of geographic atrophy: An Italian survey including 365 participants.

PURPOSE: Geographic atrophy (GA) is a severe complication of age-related macular degeneration (AMD) and leads to irreversible visual decline. To date, no effective treatment is available for GA patients. However, a number of new therapies have recently been approved and several others are in the pipeline. This rapid evolution of prospects for GA patients requires constant updating of ophthalmologists' understanding of GA and its management so as to provide the appropriate treatment. For this reason, Società Italiana di Scienze Oftalmologiche (S.I.S.O.) has designed a specific survey to gauge the position of Italian ophthalmologists in this regard. METHODS: The three hundred and sixty-five Italian ophthalmologists who agreed to take part received a seventeen-part questionnaire guaranteeing privacy and anonymity. The survey was compiled through an online portal and the results were sent directly to S.I.S.O. ETS. Two graders analyzed the data and recorded the results. RESULTS: The results showed a high level of self-assessed awareness and understanding of GA, as well as considerable willingness to further improve knowledge of the disease. Most of the participants claimed to have effective rules of conduct in place for managing GA patients, including prompt response, involving a high prevalence of nutraceutical prescriptions and lifestyle recommendations. CONCLUSIONS: This survey provided an overview of how GA patients are managed in Italy. The Italian ophthalmology community appears to be ready to adopt the upcoming treatments for GA.

Digital histology of retinal microaneurysms as provided by dense B-scan (DART) OCTA: characteristics and clinical relevance in diabetic retinopathy.

BACKGROUND: Retinal microaneurysms (MAs) are among the earliest signs of diabetic retinopathy (DR) and can be classified in several subtypes by non-invasive multimodal retinal imaging. The main aim of the present study is to characterize retinal MAs perfusion properties and their blood flow network connectivity by means of Dense Automatic-RealTime (DART) OCTA technology, checking the relationship with the multimodal retinal imaging classification and testing the clinical impact of DART. METHODS: A cross-sectional, observational study setting was chosen. Multimodal retinal imaging included confocal multicolour, OCT, OCTA and DART OCTA. We classified retinal MAs accordingly with the recently proposed multimodal retinal imaging classification and we tested the role of DART OCTA for detecting retinal MAs blood flow network connectivity. We also tested the relationship with clinical parameters. RESULTS: We included 206 retinal MAs of 36 DR eyes. We categorized retinal MAs as red (70; 34%), mixed (106; 51%) and green (30; 15%), corresponding to precise characteristics on structural OCT and both (regular) enface and DART OCTA images. The agreement between en-face and DART OCTA techniques for detecting MAs perfusion was very high (overall ICC 0.98; p < 0.01). However, DART OCTA provided clearer visualization than enface OCTA for detecting the blood flow network connectivity of retinal MAs, especially looking at the afferent and efferent MAs capillaries. Multimodal retinal imaging classification of retinal MAs provided significant correlations with DR duration, DR stage, and macular capillary non-perfusion. CONCLUSIONS: DART OCTA provided several new insights on retinal MAs characteristics and their blood flow network connectivity.

Linear streaks associated with retinitis pigmentosa.

PURPOSE: To describe a phenotypical manifestation characterized by the identification of peripheral linear streaks associated with retinitis pigmentosa (RP). METHODS: Study design is a prospective observational case series. All consecutive patients affected by RP underwent a complete ophthalmological examination. The diagnosis of peripheral linear streaks was based on the identification of curvilinear atrophic streaks in the periphery of the retina. RESULTS: Overall, six out of 140 patients (4.2%) were affected by peripheral linear streaks associated with RP. A single patient showed also punched out chorioretinal lesions at the posterior pole, with macular neovascularization development over the follow-up, treated with ranibizumab injections. CONCLUSIONS: RP phenotypical manifestation characterized by peripheral linear streaks is infrequent and may provide additional evidence to support the contribution of inflammation in the pathogenesis of RP.

Non-vasogenic cystoid maculopathy in autosomal recessive bestrophinopathy: novel insights from NIR-FAF and OCTA imaging.

BACKGROUND: Autosomal Recessive Bestrophinopathy (ARB) is an inherited retinal disease caused by biallelic mutations in the BEST1 gene. Herein, we report the multimodal imaging findings of ARB presenting with cystoid maculopathy and investigate the short-term response to combined systemic and topical carbonic anhydrase inhibitors (CAIs). MATERIAL AND METHODS: An observational, prospective, case series on two siblings affected by ARB is presented. Patients underwent genetic testing and optical coherence tomography (OCT), blue-light fundus autofluorescence (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), fluorescein angiography (FA), MultiColor imaging, and OCT angiography (OCTA). RESULTS: Two male siblings, aged 22 and 16, affected by ARB resulting from c.598C>T, p.(Arg200*) and c.728C>A, p.(Ala243Glu) BEST1 compound heterozygous variants, presented with bilateral multifocal yellowish pigment deposits scattered through the posterior pole that corresponded to hyperautofluorescent deposits on BL-FAF. Vice versa, NIR-FAF mainly disclosed wide hypoautofluorescent areas in the macula. A cystoid maculopathy and shallow subretinal fluid were evident on structural OCT, albeit without evidence of dye leakage or pooling on FA. OCTA demonstrated disruption of the choriocapillaris throughout the posterior pole and sparing of intraretinal capillary plexuses. Six months of combined therapy with oral acetazolamide and topical brinzolamide resulted in limited clinical benefit. CONCLUSIONS: We reported two siblings affected by ARB, presenting as non-vasogenic cystoid maculopathy. Prominent alteration of NIR-FAF signal and concomitant choriocapillaris rarefaction on OCTA were noted in the macula. The limited short-term response to combined systemic and topical CAIs might be explained by the impairment of the RPE-CC complex.

Quantitative Optical Coherence Tomography Detection of New Neovascular Branches and Association With Exudation Recurrence in Neovascular Age-Related Macular Degeneration.

Purpose: The purpose of this study was to investigate the clinical role of multi-signal quantitative optical coherence tomography angiography (OCTA) perfusion sampling in neovascular age-related macular degeneration (AMD). Methods: The study was designed as a cross-sectional case series. We collected data from already treated macular neovascularization (MNV), characterized by (I) clinically relevant recurrent exudation, (II) nonclinically relevant recurrent exudation, and (III) inactive lesion. We proposed a new OCTA metric, calculating the gap between high-resolution (HR) and high-speed (HS) OCTA samplings, hypothesizing that this gap might improve the detection of new secondary MNV branches, being also associated with exudation recurrence. Main outcome measures were the HR-HS gap-based categorization of MNV lesions and the assessment of its association with exudative, minimally exudative, and inactive lesions. Results: Our cohort (which consisted of 32 MNV eyes; 32 patients; mean disease duration 5 years) was classified as type 1 (17; 53%), type 2 (11; 34%), or mixed type (4; 13%) MNV. Subretinal fibrosis was found in 17 out of 32 eyes (53%), whereas outer retinal atrophy involved 22 of 32 eyes (69%). HR-HS MNV gap was significantly different among MNV subgroups: 18% for the exudative subgroup, 12% for the minimally exudative subgroup, and 4% for the inactive subgroup. HR-HS gap significantly correlated with best corrected visual acuity (BCVA), disease duration, fibrosis, and outer retinal atrophy. Conclusions: HR-HS gap is a novel quantitative metric to detect the secondary novel branches of AMD-related MNV. This parameter is clinically relevant because it is associated with fluid recurrence. The integration of HR-HS gap in artificial intelligence models might help to predict MNV reactivation and to optimize treatment strategies.

Extensive Contact Lens Wear Modulates Expression of miRNA-320 and miRNA-423-5p in the Human Corneal Epithelium: Possible Biomarkers of Corneal Health and Environmental Impact.

The identification of new biomarkers of ocular diseases is nowadays of outmost importance both for early diagnosis and treatment. Epigenetics is a rapidly growing emerging area of research and its involvement in the pathophysiology of ocular disease and regulatory mechanisms is of undisputable importance for diagnostic purposes. Environmental changes may impact the ocular surface, and the knowledge of induced epigenetic changes might help to elucidate the mechanisms of ocular surface disorders. In this pilot study, we investigated the impact of extensive contact lens (CL) wearing on human corneal epithelium epigenetics. We performed ex vivo analysis of the expression of the miR-320 and miR-423-5p involved in the processes of cellular apoptosis and chronic inflammation. The human corneal epithelium was harvested from healthy patients before the photorefractive keratectomy (PRK). The patients were divided into two age- and sex-matched groups accordingly to CL wearing history with no CL wearers used as a control. The epithelium was stored frozen in dry ice at -80 °C and forwarded for miRNA extraction; afterwards, miRNA levels were detected using real-time PCR. Both miRNAs were highly expressed in CL wearers (p < 0.001), suggesting epigenetic modifications occurring in chronic ocular surface stress. These preliminary results show the relationships between selected miRNA expression and the chronic ocular surface stress associated with extensive CL use. MicroRNAs might be considered as biomarkers for the diagnosis of ocular surface conditions and the impact of environmental factors on ocular surface epigenetic. Furthermore, they might be considered as new therapeutic targets in ocular surface diseases.

Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study.

INTRODUCTION: Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. METHODS: This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24 months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. RESULTS: We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8 years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). CONCLUSIONS: We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

Clinical and optical coherence tomography biomarkers as prognostic factors in dexamethasone intravitreal implant for diabetic macular edema.

PURPOSE: Aim of the study was to evaluate the efficacy of dexamethasone (DEX) 0.7 mg intravitreal implant in patients with diabetic macular edema (DME) and serous retinal detachment (SRD), and to study the prognostic factors on a follow up of 12 months. METHODS: Forty eyes of twenty- six patients with centre involving DME and SRD, who underwent DEX implant, were enrolled. Best-corrected visual acuity (BCVA), Swept source OCT imaging and intraocular pressure were evaluated. Central macular thickness (CMT), vitreomacular adhesion (VMA), disorganization of retinal inner layers (DRILs), hyperreflective dots (HRD), SRD and ellipsoid zone (EZ) disruption were included in the analysis at baseline and 12 months after implant. RESULTS: According to our parametric analysis, at 12 months, BVCA improvement from 48.6 ± 23.4 letters to 53.3 ± 24.5 letters was statistically significant (p = 0.04), CMT decreased from 460 ± 99.52 µm to 322.9 ± 117 µm. The presence at baseline of VMA (p = 0.01), EZ disruption (p = 0.03) and DRILs (p = 0.04), were associated with poor BCVA improvement at the end of follow-up. CONCLUSION: In conclusion, OCT biomarkers can be considered significant prognostic factors for treatment outcome in patients with DME undergoing DEX intravitreal implant.

Retinal Vessel Analysis and Microvascular Abnormalities in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

Background: Philadelphia-negative chronic myeloproliferative neoplasms are a group of clonal hematopoietic disorders including polycythemia vera, essential thrombocythemia, and primary myelofi-brosis. These neoplasms are characterized by an increased risk of thrombotic complications. Several studies have highlighted that the study of vessels of the retina offers the opportunity to visualize, in vivo, the damage to microcirculation that is common in various systemic pathologies. Methods: in our study, forty patients underwent an ophthalmological examination, using non-invasive imaging tech-niques, for analyses of their retinal vascularization. The objective was to correlate the findings ob-tained from this study of the retina with different markers of thrombotic risk, to demonstrate the usefulness of studying retinal vessels as a possible new prognostic biomarker of thrombotic risk in patients affected by Philadelphia-negative chronic myeloproliferative neoplasms. Results: retinal imaging demonstrated changes in the microcirculation, with a reduced vascular density of the deep and superficial capillary plexuses with respect to a normal group, and a correlation between retinal changes and blood parameters. Conclusions: additional research will allow us to determine whether retinal changes in individuals with chronic myeloproliferative neoplasms could be predictive of the development of thrombotic events in these subjects.