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.

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.

Optical coherence tomography (OCT) and OCT-angiography in syndromic versus non-syndromic USH2A-associated retinopathy.

PURPOSE: To compare non-syndromic and syndromic forms of USH2A-related retinitis pigmentosa (RP) by means of structural optical coherence tomography (OCT) and OCT-angiography (OCTA). METHODS: Observational, cross-sectional, multicenter study. All patients underwent best corrected visual acuity (BCVA) measurement, OCT (Spectralis HRA + OCT, Heidelberg Engineering) and OCTA (OCT DRI Topcon Triton, Topcon Corporation). We compared subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI), presence of cystroid macular edema (CME), macular vessel density (VD) at the superficial and deep capillary plexa, as well as VD of the radial peripapillary capillary (RPC) network, between syndromic and non-syndromic patients with USH2A-associated retinopathy. RESULTS: Thirty-four eyes from 18 patients (7 females) were included. Thirteen patients (72.2%) were affected by Usher syndrome type 2, whereas the remaining 5 subjects (27.8%) had non-syndromic retinitis pigmentosa (nsRP). Syndromic patients were younger than nsRP (p = 0.01) and had a worse visual acuity than those with the exclusively retinal phenotype. Patients with Usher syndrome type 2 had a higher prevalence of CME and a thicker choroid compared to nsRP, although these results were not statistically significant (p = 0.775 and p = 0.122, respectively). Similarly, none of the other quantitative OCT and OCTA parameters was statistically different between the two groups. CONCLUSIONS: Despite their younger age, patients with Usher syndrome type 2 displayed similar choroidal and microvascular changes compared to those with nsRP.

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.

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.

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.

Association of Circulating Antiretinal Antibodies With Clinical Outcomes in Retinitis Pigmentosa.

Purpose: To determine if circulating antiretinal antibodies (ARAs) differ between patients affected by retinitis pigmentosa (RP) and control participants and to assess whether ARAs are associated with clinical outcomes in patients with RP. Methods: Cross-sectional study involving a group of patients clinically diagnosed with RP and a control group of healthy participants. Serum autoantibodies against enolase, heat shock protein 70 (HSP70), and carbonic anhydrase II (CAII) were tested in all participants using Jess capillary Western blot. We compared ARA prevalence between the RP and control groups and investigated the association of serum ARA positivity with macular edema and vitreomacular disorders in patients affected by RP. Results: Thirty-six patients affected by RP and a control group of 39 healthy individuals were included. Overall, at least one ARA positivity was detected in 89% and 80% of participants in the RP and control groups, respectively. We observed a similar prevalence of anti-CAII and anti-enolase ARA between patients and controls (P = 0.87 and P = 0.35, respectively). Sera from patients with RP tested positive for anti-HSP70 ARAs more frequently than those from controls (53% vs. 36%), albeit without reaching statistical significance (P = 0.29). Among the 72 eyes with RP, 25% presented with macular edema (most often bilateral) and 33% with epiretinal membrane and/or lamellar macular hole. None of the three ARAs was associated with an increased risk of any macular complications in eyes affected by RP (all P > 0.05). Conclusions: The prevalence of circulating ARAs against enolase, HSP70, and CAII is similar between patients affected by RP and healthy individuals. Our results provide evidence against the association of ARAs with macular edema and vitreomacular interface disorders in RP.

The Localization of Intraretinal Cysts Has a Clinical Role on the 2-Year Outcome of Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the relationship between ≥ 1 localizations of intraretinal fluid (IRF) within retinal layers and the 2-year outcome in a cohort of neovascular age-related macular degeneration (AMD) eyes. DESIGN: Retrospective case series. PARTICIPANTS: Two hundred forty-three eyes of 243 AMD patients affected by type 1 and type 2 macular neovascularization (MNV). METHODS: We analyzed data considering MNV onset, 1-year, and 2-year timepoints. Optical coherence tomography images were used to classify MNV types, distinguish different types of fluids and assess IRF localization within retinal layers. A subcohort of eyes were also analyzed by OCT angiography. MAIN OUTCOME MEASURES: The association between IRF cyst localization and both visual outcome and onset of outer retinal atrophy at 2-year follow-up. RESULTS: Macular neovascularizations were distributed as type 1 (69%) and type 2 (31%). The mean number of intravitreal injections was 7 ± 2 at 1-year follow-up and 5 ± 2 at 2-year follow-up. Baseline best-corrected visual acuity was 0.4 ± 0.3 logarithm of the minimum angle of resolution, improving to 0.3 ± 0.4 at 2-year follow-up (P < 0.01). Outer retinal atrophy occurred in 24% of cases at 1 year and 39% of cases at 2-year follow-up. Intraretinal fluid localizations at the level of IPL-INL and OPL-ONL at baseline were associated with the worst functional and anatomical outcome. Moreover, the presence of IRF at baseline was associated with greater impairment of the intraretinal vascular network. CONCLUSIONS: The localization of IRF at the level of IPL-INL and OPL-ONL retinal layers represents a negative prognostic biomarker for the morphologic and functional outcomes of neovascular AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ocular surface in posterior segment surgery.

Nowadays, the technological breakthroughs of mini-invasive vitreo-retinal surgery improved the perioperative management and the outcomes of millions of patients. The most common procedures include pars plana vitrectomy, episcleral surgery, intravitreal injections, and laser photocoagulation. Potential sight and non-sight-threatening side effects have been reported during the follow-up period. Ocular surface disbalance can be induced by the aforementioned procedures, resulting in mild to severe ocular discomfort symptoms. This condition may recognize different causes such as pre-existing or concomitant diseases of the external eye, the surgical procedure damage of the anatomical or physiological structures of the ocular surface, the prolonged side effects induced by the chronic topical treatment that may be toxic to the external eye.In addition to the most frequent dry eye-related signs and symptoms, subconjunctival haemorrhages, corneal epithelium damage, partial loss of corneal sensitivity or changes in corneal nerve density could postoperatively affect our patients.In conclusion, any surgical trauma directed to the posterior segment of the eye may cause the loss of the ocular surface homeostasis. Ophthalmologists should not only recognise and treat, but possibly prevent, all patients' symptoms that could manifest in the postoperative time.

Foveal Eversion is Associated with High Persistence of Macular Edema and Visual Acuity Deterioration in Retinal Vein Occlusion.

INTRODUCTION: Foveal eversion (FE) is a recently described optical coherence tomography (OCT) finding associated with negative outcome in diabetic macular edema. The main goal of the present study was to investigate the role of the FE metric in the diagnostic workup of retinal vein occlusion (RVO). METHODS: This study was a retrospective, observational case series. We included 168 eyes (168 patients) affected by central RVO (CRVO) and 116 eyes (116 patients) affected by branch (RVO). We collected clinical and imaging data from CRVO and BRVO eyes affected by macular edema with a minimum follow-up of 12 months. On structural OCT, we classified FE as pattern 1a, characterized by thick vertical intraretinal columns, pattern 1b, presenting thin vertical intraretinal lines, and pattern 2, showing no signs of vertical lines in the context of the cystoid macular edema. For statistical purposes, we considered data collected at baseline, after 1 year and at the last follow-up. RESULTS: The mean follow-up was 40 ± 25 months for CRVO eyes and 36 ± 24 months for BRVO eyes. We found FE in 64 of 168 CRVO eyes (38%) and in 25 of 116 BRVO eyes (22%). Most of the eyes developed FE during the follow-up. For CRVO eyes, we found 6 eyes (9%) with pattern 1a, 17 eyes (26%) with pattern 1b and 41 eyes (65%) with pattern 2. Of those BRVO eyes with FE, we found 8 eyes (32%) with pattern 1a + 1b and 17 eyes (68%) with pattern 2. In both CRVO and BRVO the presence of FE was significantly associated with higher persistence of macular edema and worse outcome, with FE pattern 2 representing the most severe condition. Remarkably, FE patterns 1a and 1b were characterized by BCVA stability over the follow-up, whereas FE pattern 2 showed significant bestcorrected visual acuity (BCVA) worsening at the end of the follow-up. CONCLUSIONS: FE can be considered a negative prognostic biomarker in RVO, associated with higher persistence of macular edema and worse visual outcome. Müller cell impairment might represent the pathogenic mechanism leading to the loss of macular structural support and impairment of fluid homeostasis.

HYPERREFLECTIVE BAND IN THE GANGLION CELL LAYER IN RETINITIS PIGMENTOSA.

PURPOSE: To describe a sign that takes the form of a continuous hyperreflective band within the thickness of the ganglion cell layer (GCL), thus dubbed the "hyperreflective ganglion cell layer band" (HGB), which the authors detected in a fraction of patients affected by retinitis pigmentosa (RP). METHODS: Retrospective, cross-sectional, observational study. Optical coherence tomography (OCT) images of patients with RP examined between May 2015 and June 2021 were retrospectively reviewed for the presence of HGB, epiretinal membrane (ERM), macular hole, and cystoid macular edema (CME). The ellipsoid zone (EZ) width was also measured. A subgroup of patients underwent microperimetry in the central 2°, 4°, and 10°. RESULTS: One hundred and fifty-four eyes from 77 subjects were included in the study. The HGB was present in 39 (25.3%) eyes with RP. Mean best-corrected visual acuity (BCVA) was 0.39 ± 0.05 logMAR (approximately 20/50 Snellen equivalent) and 0.18 ± 0.03 logMAR (approximately 20/32 Snellen equivalent) in eyes with and without HGB, respectively ( P < 0.001). The two groups did not differ regarding EZ width; mean 2°, 4°, and 10° retinal sensitivity; and prevalence of CME, ERM, and macular hole. The multivariable analysis showed the presence of HGB to be a predictor of poorer BCVA ( P < 0.001). CONCLUSION: HGB is an OCT finding detectable in approximately a quarter of eyes with RP and is associated with a poorer visual function. In the discussion, the authors speculate about possible morphogenetic scenarios to explain this observation.

Characterizing macular edema in retinitis pigmentosa through a combined structural and microvascular optical coherence tomography investigation.

The aim of the study was to characterize macular edema (ME) in retinitis pigmentosa (RP) by means of quantitative optical coherence tomography (OCT)-based imaging. The study was designed as observational, prospective case series, with 1-year follow-up. All RP patients underwent complete ophthalmologic assessment, including structural OCT, OCT angiography, and microperimetry (MP). The primary outcome was the characterization through quantitative OCT-based imaging of RP eyes complicated by ME. A total of 68 RP patients' eyes (68 patients) and 68 eyes of 68 healthy controls were recruited. Mean BCVA was 0.14 ± 0.17 LogMAR at baseline and 0.18 ± 0.23 LogMAR at 1-year follow-up (p > 0.05). Thirty-four eyes (17 patients; 25%) showed ME, with a mean ME duration of 8 ± 2 months. Most of the eyes were characterized by recurrent ME. The ME was mainly localized in the inner nuclear layer in all eyes. LogMAR BCVA was similar in all RP eyes, whether with or without ME, although those with ME were associated with higher vessel density values, as well as thicker choroidal layers, than those without ME. In conclusion, the inner retina is closely involved in the pathogenesis of ME. The impairment of retinal-choroidal exchanges and Müller cell disruption might be a major pathogenic factor leading to the onset of ME in RP.

HYPERREFLECTIVE FOCI PRECEDE MACULAR NEOVASCULARIZATION FORMATION IN ANGIOID STREAKS.

PURPOSE: To describe the steps leading to the development and progression of macular neovascularization (MNV) in angioid streaks. METHODS: The study was designed as retrospective, longitudinal case series. Patients with angioid streaks were investigated by means of multimodal imaging, including fundus autofluorescence and structural optical coherence tomography. Main outcome measures were hyperreflective foci and MNV progression steps. RESULTS: Overall, 40 eyes (20 patients) affected by angioid streaks were evaluated. Over the follow-up, five eyes of five patients developed MNV. The mean follow-up was of 1.6 years. The mean number of anti-vascular endothelial growth factor injections was 4.35 ± 1.4. Mean best-corrected visual acuity was 0.53 ± 0.38 LogMAR at the MNV onset, improving to 0.42 ± 0.40 LogMAR at the end of the follow-up ( P > 0.05). Intraretinal hyperreflective foci onset and coalescence represented the first alterations occurring before the onset of the MNV. Anti-vascular endothelial growth factor treatment was associated with exudation relapsing and remitting, with still present intraretinal hyperreflective foci and pigment accumulation. The longitudinal analysis of our cohort of eyes outlined the event timeline: 1.2 months to find concentrated hyperreflective foci, 4.5 months to observe pigment organization through the outer nuclear layer, and 1.5 years to detect MNV. CONCLUSION: Hyperreflective foci formation, concentration, and migration represent early alterations occurring before the onset of the MNV in angioid streaks.

Foveal eversion patterns in diabetic macular edema.

The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and the outcome. The study was designed as prospective, observational, with two years of follow-up. DME patients were divided in two groups, one treated by combined anti-VEGF injections and dexamethasone (DEX) implants, and the other treated by fluocinolone acetonide (FAc) implant with additional anti-VEGF retreatments if needed. Main outcome measures were foveal eversion prevalence, foveal eversion patterns, best-corrected visual acuity (BCVA), central macular thickness (CMT), structural OCT metrics, number of intravitreal injections. One hundred and forty-six eyes (146 patients; 80 males; mean age 67 ± 8 years) affected by already treated DME, with 84 eyes treated with anti-VEGF/DEX treatments (mean of 10 ± 3 injections) and 62 treated with FAc implant. Looking at the treatments administered before the inclusion into the study, 84 eyes (58%) were treated with anti-VEGF injections, whereas 62 eyes (42%) underwent a combination of anti-VEGF and corticosteroids implants. DME eyes showed statistically significant improvements of LogMAR BCVA and CMT over the 2-year follow-up. Foveal eversion was found in 83 eyes (57%), categorized as follows: Pattern 1a (16;19%); Pattern 1b (22;27%) and Pattern 2 (45;54%). BCVA improvement was detected in all the subgroups, excepting for Pattern 2, which showed also significantly worse structural OCT parameters. Pattern 1b and Pattern 2 were characterized by significantly higher prevalence of persistent DME (64% and 89% of cases, respectively). Foveal eversion patterns were correlated with progressively worse DME outcome. Foveal eversion may be associated to the loss of foveal homeostasis, with consequent poor response to intravitreal treatments and worse DME outcome.

Multimodal imaging evaluation of occult macular dystrophy associated with a novel RP1L1 variant.

Purpose: Occult Macular Dystrophy (OMD) is an autosomal dominant inherited retinal dystrophy caused by mutations in the retinitis pigmentosa 1-like 1 (RP1L1) gene. The present study describes a novel RP1L1 variant, identified for the first time in two Italian sisters diagnosed with OMD, along with multimodal imaging features, including Optical Coherence Tomography (OCT) Angiography. Methods: We performed multimodal imaging including spectral-domain OCT, blue light autofluorescence (BAF), infrared autofluorescence (IRAF), swept-source OCT Angiography (OCTA), full-field and multifocal electroretinography. Genetic analysis was performed using Next-Generation Sequencing. Pathogenic potential of nonsynonymous novel variants was scored with two in silico algorithms. Results: Proband 1 (P1) and proband 2 (P2) were two Italian sisters of 61 and 56 years old. Both reported a history of progressive visual loss without fundoscopic alterations. P1 reported a 4-year history of rapid visual function worsening, and her best-corrected visual acuity (BCVA) was counting fingers in both eyes. P2 reported a 20-year history of mild but progressive visual acuity loss, and her BCVA was 1/10 and 2/10 respectively in her right and left eye. Structural OCT displayed disorganization of outer retinal bands at the macula and foveal cavitation; loss of foveal photoreceptors was remarkably evident on en-face OCT slabs. OCTA quantitative analysis found that vessel density was reduced both at SCP and DCP while choriocapillaris blood flow was relatively spared. Genetic analysis found the same rare dominant c.2873G > C, p.Arg958Pro variant in the RP1L1 gene. The substitution was regarded as moderately radical according to Grantham score while PolyPhen2 classified the amino acidic substitution as probably damaging. Conclusions and importance: Our study expands the mutational spectrum of RP1L1 gene: the rare c.2873G > C, p.Arg958Pro missense variant may be considered a new pathogenic variant for OMD, the first to be identified exclusively in an Italian family. Moreover, our quantitative OCTA data suggest that OMD is characterized by a rarefaction of superficial and deep capillary plexus.

VEGF-targeting drugs for the treatment of retinal neovascularization in diabetic retinopathy.

Diabetic retinopathy (DR) is the most common microangiopathic complication of diabetes mellitus, representing a major cause of visual impairment in developed countries. Proliferative DR (PDR) represents the last stage of this extremely complex retinal disease, characterized by the development of neovascularization induced by the abnormal production and release of vascular endothelial growth factor (VEGF). The term VEGF includes different isoforms; VEGF-A represents one of the most important pathogenic factors of DR. Anti-VEGF intravitreal therapies radically changed the outcome of DR, due to combined anti-angiogenic and anti-edematous activities. Nowadays, several anti-VEGF molecules exist, characterized by different pharmacological features and duration. With respect to PDR, although anti-VEGF treatments represented a fundamental step forward in the management of this dramatic complication, a big debate is present in the literature regarding the role of anti-VEGF as substitute of panretinal photocoagulation or if these two approaches may be used in combination. In the present review, we provided an update on VEGF isoforms and their role in DR pathogenesis, on current anti-VEGF molecules and emerging new drugs, and on the current management strategies of PDR. There is an overall agreement regarding the relative advantage provided by anti-VEGF, especially looking at the management of PDR patients requiring vitrectomy, with respect to laser. Based on the current data, laser approaches might be avoided when a perfectly planned anti-VEGF therapeutic strategy can be adopted. Conversely, laser treatment may have a role for those patients unable to guarantee enough compliance to anti-VEGF injections.Key messagesVEGF increased production, stimulated by retinal hypoperfusion and ischaemia, is a major pathogenic factor of neovascular complication onset in diabetic retinopathy and of DR stages progression.Nowadays, several anti-VEGF molecules are available in clinical practice and other molecules are currently under investigation. Each anti-VEGF molecule is characterized by different targets and may interact with multiple biochemical pathways within the eye.All the data agreed in considering anti-VEGF molecules as a first line choice for the management of diabetic retinopathy. Laser treatments may have a role in selected advanced cases and for those patients unable to guarantee enough compliance to intravitreal treatments schemes.

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN CENTRAL RETINAL VEIN OCCLUSION COMPLICATING AMYLOID LIGHT-CHAIN AMYLOIDOSIS.

PURPOSE: To describe a case of paracentral acute middle maculopathy associated with central retinal vein occlusion in a patient affected by amyloid light-chain amyloidosis. METHODS: One patient with confirmed diagnosis of amyloid light-chain amyloidosis, displaying paracentral acute middle maculopathy and central retinal vein occlusion, was recruited. The patient underwent complete ophthalmologic examination and multimodal imaging, including: fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. RESULTS: Fundus autofluorescence showed a ferning pattern, corresponding to linear hypofluorescence in late-phase indocyanine green angiography and delayed venous filling, detected by fluorescein angiography. Structural optical coherence tomography revealed a hyper-reflective line located in the outer plexiform layer, corresponding to the prominent middle limiting membrane, along with several placoid lesions. Optical coherence tomography angiography found that the superficial capillary plexus was preserved, whereas vessel density was reduced in both the deep capillary plexus and the choriocapillaris. After 1 year of follow-up, the patient achieved an almost complete morphological recovery. CONCLUSION: Multimodal imaging described in depth the morphological features of a case of combined paracentral acute middle maculopathy and central retinal vein occlusion in a patient affected by amyloid light-chain amyloidosis.

IMMUNOGLOBULIN G4-RELATED OPHTHALMIC DISEASE MIMICKING INTRAOCULAR LYMPHOMA: A CASE REPORT.

PURPOSE: To describe a case of immunoglobulin G4-related choroiditis mimicking intraocular lymphoma. METHODS: The patient underwent a complete ophthalmological evaluation including multimodal imaging, with structural optical coherence tomography, fluorescein angiography, indocyanine green angiography, ultra-widefield color, and autofluorescent fundus photographies to assess the ocular involvement. RESULTS: Patient's best-corrected visual acuity was of 20/25 in the right eye and 20/20 in the left eye. Fundus appearance showed abnormal yellowish choroidal lesions and moderate vitritis in both eyes. Fluorescein angiography was within normal limits, whereas indocyanine green angiography showed areas of choroiditis in both eyes, and structural optical coherence tomography scans disclosed retinal small roundish lesions in the corresponding regions. Laboratory examinations and lymph node biopsy led to the final diagnosis of immunoglobulin G4-related disease. CONCLUSION: We describe a case of immunoglobulin G4-related choroiditis mimicking intraocular lymphoma. The proper use of multimodal imaging associated with laboratory investigations was helpful to reach the correct diagnosis.

Quantitative biometric cutoffs for the choice of the intraocular lens power calculation formula for a recently introduced nondiffractive extended depth-of-focus intraocular lens.

PURPOSE: This study aimed to analyze biometry values cutoffs for the choice of the best intraocular lens power calculation formula for AcrySof IQ Vivity intraocular lens. METHODS: The study was designed as interventional case series with 3 months of follow-up. Intraocular lens power calculation formulas included Barrett Universal II and SRK/T. The first was adopted for the intraocular lens power choice. The quantitative analysis focused on the identification of specific biometric cutoffs considering axial length, anterior chamber depth, and corneal powers. We included only the dominant eye in the statistical analysis. RESULTS: One hundred and eight eyes of 54 patients (23 males; mean age 62 ± 5 years) with no ocular diseases were included. Best-corrected visual acuity improved from 0.3 ± 0.2 to 0.0 ± 0.0 logMAR. All the eyes reached spectacles-free far and intermediate visions; a spherical addition of + 1.0D was necessary to adjust near vision. We identified significant quantitative cutoffs based on axial length and anterior chamber depth. Barrett Universal II resulted the best formula for eyes disclosing an axial length >25 mm, whereas SRK/T turned out to be the best choice for the eyes characterized by an anterior chamber depth <2.8 mm. Our analysis disclosed an overall sensitivity of 0.8 and a specificity of 0.7 (p < 0.01). CONCLUSIONS: Axial length and anterior chamber depth influence the choice of Barrett Universal II and SRK/T formulas. Quantitative biometric cutoffs may be useful to discriminate the best formula to be adopted.

Early DMO: a predictor of poor outcomes following cataract surgery in diabetic patients. The DICAT-II study.

BACKGROUND: The prospective DIabetes and CATaract Study II (DICAT II) was performed to characterise the risks of cataract surgery to the retinae of patients with early diabetic macular oedema (E-DMO). METHODS: DICAT II was a prospective, comparative, multicentre, observational study involving six Italian clinics. Patients were aged ≥55 years, had type 1 or 2 diabetes with spectral-domain optical coherence tomography evidence of ESASO classification Early DMO. Group 1 eyes (78 eyes, 78 patients) underwent phacoemulsification-based cataract surgery. Group 2 eyes (65 eyes, 65 patients) had E-DMO and either clear media or had undergone uncomplicated cataract surgery ≥1 year previously. Central subfield thickness (CST) and best-corrected visual acuity (BCVA) were assessed in both groups. RESULTS: The negative impact of surgery on CST was evident after the first postoperative week; CST peaked during the first month, then rapidly decreased. CST worsening ≥10 µm was observed in 63/78 eyes (80.7%) and 29/65 eyes (44.6%) in Groups 1 and 2, respectively (p < 0.0001). CST worsening of ≥50 µm was observed in 51 eyes (65.4%) and 10 eyes (15.4%) in Groups 1 and 2, respectively (p < 0.0001). Mean CST worsening was lower in Group 2 than in Group 1 (38.6 ± 30.4 µm vs 85.5 ± 55.3 µm, p < 0.0001) with a lower BCVA loss (-2.6 ± 3.5 letters vs -8.2 ± 6.2 letters, p < 0.0001). Higher glycaemic levels and HBA1c levels were significantly associated with the risk of >50 µm CST worsening in eyes from both groups. CONCLUSION: Early DMO is associated with poorer outcomes after cataract surgery and requires close pre- and postoperative monitoring.