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Purpose: To analyse the longitudinal changes in imaging parameters in eyes with acute or chronic central serous chorioretinopathy (CSCR)., Methods: This was a multicentric, retrospective, longitudinal, observational study in patients with a diagnosis of CSCR and having at least 4 years of follow-up. Trend in choroidal thickness (CT), area of double layer sign (DLS), area of retinal pigment epithelium (RPE) alterations, and area of hyper-autofluorescence were analysed., Results: A total of 175 eyes of 146 patients with a mean age of 52.9 ± 12.5 years were included. Fifty-two eyes had acute and 123 had chronic CSCR at baseline. There was an overall decreasing trend of CT values during follow up (from 354.4 ± 74.8 at baseline to 343.2 ± 109.4 at final visit). There was a steady rise in DLS width and RPE alteration in the overall cohort (from 811.7 ± 760.6 microns and 3.5 ± 3.3 disc areas respectively at baseline to 1209.1 ± 1113.18 microns, 4.1 ± 3.6 disc areas at final visit). An initial rise in hyper-autofluorescent area followed by steady fall was seen in chronic CSCR. A significant positive correlation (r = 0.54, p = 0.004) was seen between change in DLS width and change in area of hyper-autofluorescence. On linear regression analysis, lower CMT and absence of intraretinal fluid at baseline were associated with greater increase in RPE abnormalities., Conclusion: Acute and chronic CSCR had different pattern of change in imaging parameters with area of RPE alterations in acute CSCR not reaching values close to that of chronic CSCR eyes even after long follow up., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To explore changes in reticular pseudodrusen (RPD) number and location after the development of macular neovascularization (MNV) in eyes with prior intermediate age-related macular degeneration, focusing on different retinal regions differently affected by MNV., Methods: This retrospective longitudinal study included intermediate age-related macular degeneration eyes with RPD that developed MNV. Reticular pseudodrusen were assessed at baseline when MNV was diagnosed (MNV stage) and after anti-vascular endothelial growth factor treatment. Three regions of interest were considered: MNV area, subretinal fluid (SRF) area, and a marginal area of 1,000 µm around SRF (marginal zone). Reticular pseudodrusen counts were compared with age- and sex-matched control eyes with RPD that did not develop MNV., Results: Reticular pseudodrusen number exhibited a significant decrease after MNV development in the MNV area (P = 0.048) and in the area with SRF (P = 0.078). A statistically significant decrease was also disclosed in the marginal area around SRF (P = 0.002), associated with larger SRF areas. Control eyes did not show any significant change in the RPD count., Conclusion: Reticular pseudodrusen reduction after MNV development suggests a complex interplay involving the MNV itself, the presence of SRF, and trophic changes. The results of this study highlight the role of MNV in retinal nutritional balance and provide intriguing results in the RPD life cycle.

Purpose: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient., Case Description: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision., Discussion: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity., Conclusion: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with dry AMD (d-AMD) leading to geographic atrophy (GA) and significant visual impairment. Multimodal imaging plays a crucial role in d-AMD diagnosis and management, allowing for detailed classification of patient phenotypes and aiding in treatment planning and prognosis determination. Treatment approaches for d-AMD have recently witnessed profound change with the development of specific drugs targeting the complement cascade, with the first anticomplement agents recently approved for GA treatment. Additionally, emerging strategies such as gene therapy and laser treatments may offer potential benefits, though further research is needed to fully establish their efficacy. However, the lack of effective therapies capable of restoring damaged retinal cells remains a major challenge. In the future, genetic treatments aimed at preventing the progression of d-AMD may emerge as a powerful approach. Currently, however, their development is still in the early stages., (© 2024. The Author(s).)

Objective: This study was aimed primarily at describing the results of aqueous real-time polymerase chain reaction (RT-PCR) and reporting the rate of therapeutic modifications directly attributable to this procedure (profitability). Our secondary outcome was to compare demographic and clinical characteristics between patients with RT-PCR positivity and those with RT-PCR negative results., Design: Retrospective observational study conducted at the Uveitis Service of San Raffaele Hospital (Milan, Italy) between November 2016 and July 2022., Participants: Patients with infectious uveitis suspect (anterior, intermediate, posterior uveitis, or panuveitis)., Methods: Patients with suspected infectious uveitis underwent aqueous RT-PCR for detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Toxoplasma gondii., Results: Sixty-five eyes of 61 patients (60 ±16 years of age; 54% males) were included. Aqueous RT-PCR tested positive in 58% and negative in 42% of patients. CMV and HSV-1 were the most frequently detected pathogens. RT-PCR confirmed clinical suspicion in 38% of patients and altered the presumed etiologic diagnosis and treatment in 20% of patients. Profitability was associated with CMV positivity. HSV-1 positivity was related to iris atrophy. CMV positivity was correlated with keratic precipitates. Vitritis and retinitis were related to VZV, CMV, and T. gondii detection. Synechiae, retinitis, and neuritis were related to positive tests regardless of the pathogen investigated. Early complications related to paracentesis were rarely reported., Conclusion: Aqueous RT-PCR was a safe semi-invasive tool to confirm a presumptive diagnosis and to change initial suspicion in ambiguous cases of herpetic uveitis. Thus aqueous RT-PCR may alter therapeutic management., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To report a case of anatomic closure and functional improvement in a patient affected by refractory full-thickness macular hole (FTMH) undergone a combined 41-gauge (g) surgically induced macular detachment and free internal limiting membrane (ILM) flap technique., Methods: This is a retrospective case-report of a 70-years-olded woman affected by refractory FTMH who referred to Ophthalmology Unit of Guglielmo da Saliceto Hospital, Piacenza (Italy) in April 2023. The patient underwent a combined 41-g surgically induced macular detachment and free ILM flap. Macular detachment was induced by multiple subretinal injections of balanced salt solution (BSS) by 41-g needle through three retinotomies. Spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA) were performed preoperatively and postoperatively at 7th day, 1st and 6th month., Results: On 7th postoperative day, FTMH showed complete closure. BCVA improved from preoperative 20/400 to 20/70 at 6th postoperative month., Discussion: BSS subretinal injection allowed the mobilization and relaxation of retina at the posterior pole. Although the edges of the hole were still detectable, their diameters were inferior to preoperative measurements. Autologous free ILM flap allowed to fill the residual gap into the hole., Conclusion: The final anatomic closure, and the postoperative functional improvement demonstrated the effectiveness of this approach, supporting its indication for refractory FTHM.

Objectives: To characterize acquired vitelliform lesions associated with leptochoroid (i.e., diffuse choroidal thinning) and reticular pseudodrusen (RPD) and compare this phenotype to the acquired vitelliform lesion (AVL) in the dystrophic spectrum., Methods: This retrospective, observational case-control study enrolled 56 patients (56 eyes) affected by vitelliform lesions (AVL), including 27 patients with AVL associated with RPD and leptochoroid (i.e., choroidal thinning) referred to as LeptoVitelliform Maculopathy (LVM), and 29 AVL patients without other funduscopic abnormalities. The main structural features analysed were the integrity of the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), the presence of hyporeflective spaces, and hypertransmission. Choroidal vascular index (CVI) was calculated using ImageJ software., Results: Patients with LVM were 6.69 years older and presented smaller vitelliform lesions considering both vertical (P < 0.001) and horizontal diameters (P < 0.001) with a similar visual impairment compared to the AVL group (P = 0.27). The LVM subgroup showed a greater alteration of the ELM (p < 0.001) and choroidal hypertransmission (i = 0.007), accompanied by less frequent RPE bumps (P = 0.001) and hyporeflective spaces within the vitelliform material (P = 0.002). Furthermore, the LVM group presented a lower CVI with a significant attenuation on both the luminal and stromal compartments compared to AVL (P < 0.001, both)., Conclusions: The phenotypic combination of subretinal vitelliform lesion and RPD may delineate a distinct phenotype that shares with AVL only the presence of vitelliform material and a similar visual deterioration. The presented findings of LVM highlight significant structural and microvascular alterations that may hold prognostic relevance, warranting future longitudinal studies., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: To characterize clinical and prognostic implications of leptovitelliform maculopathy (LVM), a distinctive phenotype of vitelliform lesion characterized by the coexistence of subretinal drusenoid deposits (SDDs) and leptochoroid., Design: Retrospective, cohort study., Subjects: The study compared patients affected by LVM with cohorts displaying a similar phenotypic spectrum. This included patients with acquired vitelliform lesions (AVLs) and those with SDDs alone., Methods: A total of 60 eyes of 60 patients were included, of which 20 eyes had LVM, 20 eyes had AVLs, and the remaining had SDDs. Patients >50 years of age with complete medical records and multimodal imaging for ≥6 months of follow-up, including color fundus photography or MultiColor imaging, OCT, fundus autofluorescence, and OCT angiography were included., Main Outcome Measures: Choroidal vascularity index (CVI); proportion of late-stage complications (macular neovascularization, atrophy)., Results: The AVL subgroup exhibited a significantly higher CVI compared with both LVM (P = 0.001) and SDD subgroups (P < 0.001). The proportion of late-stage complications significantly differed among subgroups (chi-square = 7.5, P = 0.02). Eyes with LVM presented the greatest proportion of complications (55%) after a mean of 29.3 months, whereas the remaining eyes presented a similar proportion of complications, including 20% in the AVL group after 27.6 months and 20% in the SDD group after 36.9 months. Kaplan-Meier estimates of survival demonstrated a significant difference in atrophy development between groups (P < 0.001), with a median survival of 3.9 years for the LVM group and 7.1 years for controls. The presence of LVM correlated with a fourfold increase in the likelihood of developing complications., Conclusions: Leptovitelliform maculopathy, characterized by the association of vitelliform lesions with SDDs and leptochoroid, represents a distinct clinical phenotype in the broader spectrum of vitelliform lesions. The importance of a clinical distinction for these lesions is crucial due to their higher propensity for faster progression and elevated rate of complications, particularly atrophic conversion., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the impact of optical coherence tomography phenotypes preceding atrophy related to age-related macular degeneration on the progression of atrophic lesions., Methods: In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate age-related macular degeneration with a minimum follow-up of 24 months were included. The atrophy was quantified using fundus autofluorescence, also considering the directionality of atrophy as centrifugal and centripetal progression rates. The main outcome measures were geographic atrophy (GA) progression rate (mm 2 /year) and square root transformation of GA (mm 2 /year)., Results: The best-fit model for GA (odds ratio: 1.81, P < 0.001) and square root transformation of GA (odds ratio: 1.36, P < 0.001) areas revealed that the main baseline predictor was the presence of a retinal pigment epithelium-basal lamina-Bruch membrane splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (odds ratio: 0.52, P < 0.001) when considered with other confounders., Conclusion: A thin retinal pigment epithelium-basal lamina-Bruch membrane splitting without evidence of neovascularization on optical coherence tomography angiography likely represents an optical coherence tomography signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.

Purpose: To analyze the progression of structural and functional retinal impairment in type 1 diabetes mellitus (T1DM) patients with no clinical signs of diabetic retinopathy (DR) during a 3-year follow-up., Methods: This was an observational longitudinal study. Post-pediatric T1DM patients without clinical signs of DR, and sex- and age-matched healthy subjects were recruited at San Raffaele Hospital (Milan, Italy). Each patient underwent a comprehensive ophthalmological evaluation, including optical coherence tomography (OCT), OCT-angiography (OCT-A), retinal static and dynamic vessel analysis (DVA), and microperimetry., Results: 21 eyes of 21 T1DM patients (10 females; 24 ± 2 years old), and 21 age and sex-matched healthy subjects were enrolled. At baseline, T1DM eyes revealed a significantly decreased vessel length density using OCT-A (p < 0.001 and p = 0.046 in 3 × 3 and 6 × 6 mm images) and a significantly increased vessel density index (p = 0.013 and p = 0.087 in 3 × 3 and 6 × 6 mm images) of deep capillary plexus. DVA detected a significantly decreased vessel response to flicker light (p = 0.002). A significantly increased thickness of ganglion cellular layer 6-mm-diameter subfields in inferior and superior quadrants was found in diabetic patients (p < 0.001 in both subfields). At 3-years-follow-up no significant longitudinal changes were disclosed in all analyses., Conclusions: Concomitant subclinical microvascular and neurodegenerative damages could be early signs of DR onset that precede functional alterations and clinical signs of DR development. These alterations demonstrated a stable trend over time., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Introduction: To characterize the response to antivascular endothelial growth factor (VEGF) treatment of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) with subclinical angioid streaks (AS) during a 2-year follow-up., Methods: Retrospective, longitudinal, case-control, and multicentric study. Among a cohort of neovascular AMD population, we selected patients with subclinical AS and treatment-naïve MNV treated with anti-VEGF for a 2-year follow-up. An age- and sex-matched control group with treatment-naïve MNV secondary to AMD without subclinical AS was selected. Demographics and differences in treatment response (i.e., number of injections needed, anatomical and functional outcomes) between the two groups were analyzed., Results: Among 102 eyes of 102 patients with neovascular AMD, 34 eyes of 34 patients (82 ± 6 years old) were included in the subclinical AS group, whereas 68 eyes of 68 patients (81 ± 6 years old, p = 0.342) in the control group. All eyes with subclinical AS presented RPD compared to 56% of eyes without subclinical AS (p < 0.001). During the 2-year follow-up, eyes with subclinical AS needed more injections (10.6 ± 3.2 vs 8.3 ± 3.1 injections for eyes with and without subclinical AS, respectively, p < 0.001). Visual acuity (VA) decreased during the treatment (from 0.53 ± 0.37 at the baseline to 0.69 ± 0.45 LogMAR at 2-year follow-up, p = 0.044) in eyes with subclinical AS; no VA changes were observed in the control group (p = 0.798). RPE atrophy at the end of the 2-year follow-up affected 74% of cases with subclinical AS and 29% of cases of the control group (p < 0.001)., Conclusions: MNVs secondary to AMD with subclinical AS are characterized by worse functional and anatomical outcomes after 2-year anti-VEGF treatment compared to MNV secondary to AMD without subclinical AS, supporting the different pathophysiological mechanisms involved in this recently described AMD phenotype., (© 2024. The Author(s).)

Purpose: To report a case of exudative perifoveal exudative vascular anomalous complex (ePVAC) in a Brazilian healthy patient that underwent a complete resolution after aflibercept intravitreal injections., Case Description: A 41-year-old healthy Brazilian man complained of acute central vision loss in his right eye (RE). Fundus examination showed a perifoveal hemorrhagic aneurysmal lesion, accompanied by several hard exudates in RE. On fluorescein angiography, these abnormalities showed a progressive hyperfluorescence with surrounding leakage. Optical coherence tomography (OCT) revealed a deep, perifoveal hyporeflective cystic space with a hyperreflective wall and hyperreflective material inside of fibrin-like aspect. Around this aneurism, intraretinal hyporeflective spaces suggestive of exudation were detected. Nor pathological flow signal, or telangiectatic dilations were evidenced on OCT-angiography. Therefore, a diagnosis of exudative ePVAC in RE was hypothesized. After an initial observation, the patient underwent three monthly aflibercept intravitreal injections (0.05 ml/2 mg), with a significative anatomical and functional improvement after two weeks from first dose. On last follow-up at five months from baseline, patient experienced no evidence of new exudation and a stable visual acuity., Discussion: Placental growth factor (PlGF) may impact on pericytes' dropout, and thus on ePVAC development. In contrast to the other anti-VEGF drugs, aflibercept is the only molecule contrasting PlGF. Therefore, aflibercept would act on ePVAC not as an anti-VEGF drug, but rather as an anti-PlGF one., Conclusion: This report encouraged the use of aflibercept as a therapeutic option for ePVAC. Further studies are required to confirm our result and the impact of PlGF on ePVAC pathogenesis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In the last decade, optical coherence tomography angiography (OCTA) has become part of the clinical management of retinal vein occlusion (RVO), proving in itself a useful technique for both the prediction of visual acuity (VA) outcomes and the risk of complications. In fact, OCTA has been proven a valid imaging technique in detailed assessment of foveal and parafoveal microvascular status in both acute and chronic RVO. Quantitative OCTA data have shown a significant correlation not only with final VA but also with the extension of peripheral ischemia, which represents a major risk factor for macular edema recurrence and neovascularization onset. Finally, wide-field OCTA represents a promising noninvasive technique for the assessment of peripheral ischemia. The aim of this review is to report the main literature findings about microvascular changes and clinical applications of OCTA in the context of RVO-induced peripheral ischemia., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Saudi Journal of Ophthalmology.)

Optical coherence tomography angiography (OCTA) has extensively enhanced our comprehension of eye microcirculation and of its associated diseases. In this narrative review, we explored the key concepts behind OCTA, as well as the most recent evidence in the pathophysiology of age-related macular degeneration (AMD) made possible by OCTA. These recommendations were updated since the publication in 2020, and are targeted for 2023. Importantly, as a future perspective in OCTA technology, we will discuss how artificial intelligence has been applied to OCTA, with a particular emphasis on its application to AMD study., (© 2024. The Author(s).)

Purpose: To identify the baseline predictors of anti-VEGF treatment response at 3 years in patients affected by choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSCR)., Methods: In this retrospective longitudinal study, medical records of patients diagnosed with CNV secondary to CSCR and treated using anti-VEGF injections between April 2015 and May 2020 were reviewed. The potential qualitative and quantitative predictors of treatment response were identified or measured based on the multimodal imaging examination available for each patient at the baseline, including structural OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT-angiography (OCT-A). Univariate and multivariate analyses were performed., Results: Twenty-nine eyes from 29 patients affected by CNV complicating CSCR were included in the study. At the end of the 3-year follow-up, the mean BCVA was 20/50 Snellen equivalent (0.38 ± 0.36 LogMAR), and no significant difference with baseline BCVA (0.37 ± 0.29 LogMAR) was found (p = 0.9). Twenty out of 29 eyes (69%) had active lesions at the end of the follow-up. At multivariate analysis, none of the included features was independently associated with the 3-year BCVA outcome. Pigment epithelium detachment (PED) height (ß = 0.017, p = 0.028) and outer limiting membrane (OLM) preservation at the fovea (ß = -5.637, p = 0.026) were independently associated with the CNV activity at 3 years., Conclusion: PED height and OLM obliteration at the fovea might be considered baseline predictors of lesion activity at 3-year follow-up in patients with CNV secondary to CSCR treated with anti-VEGF therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To detect retinal neovascularization elsewhere (NVE), of the optic disc (NVD) and intraretinal microvascular abnormalities (IRMA) in treatment naive diabetic retinopathy (DR) and compare these findings by using 90° Wide-Field Colour Fundus Photography (WF CFP), Wide-Field Spectral-Domain Optical Coherence Tomography Angiography (OCTA) and the combination of WF CFP and OCTA through overlay software., Methods: Patients with treatment naive severe non-proliferative DR or proliferative DR were prospectively enrolled. All patients underwent WF-CFP and OCTA in the same day. Two readers independently analysed WF-CFP, SD-OCTA and the overlay of the two techniques. The degree of agreement between the two raters and between different techniques (WF CFP, OCTA, WF CFP combined to OCTA) were measured with Cohen's Kappa coefficient., Results: Thirty-one eyes from 21 patients (10 males, mean age 63 ± 15 years) were included. Inter-rater agreement by using WF-CFP in detection of NVE, NVD and IRMA was respectively 0.62, 0.22 and 0.55. OCTA scored values of inter-rater agreement of 0.86, 0.87 and 0.92 in detection of NVE, NVD and IRMA, respectively. By combining WF-CFP and SD-OCTA, inter-rater agreement in detection of NVE, NVD and IRMA was 0.93, 0.94 and 0.89, respectively., Conclusion: Inter-rater agreement in detection of NVE, NVD and IRMA was substantial, fair and moderate, respectively. OCTA provided almost perfect values of inter-rater agreement in NVE, NVD and IRMA detection. Combining WF-CFP and OCTA further empowered concordance values in detection of NVE and NVD. Combining OCTA and WF-CFP is the best performance to detect NVE and NVD., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Beauveria bassiana is a filamentous fungus commonly used as an insecticide that rarely causes keratitis., Methods: Patients affected by Beauveria bassiana keratitis were retrospectively recruited at San Raffaele Hospital (Milan, Italy) between 2020 and 2022. All subjects underwent comprehensive ophthalmic evaluation, including in vivo confocal microscopy (IVCM) and microbiologic examination of corneal scrapings. Beauveria bassiana was identified using 18S rDNA targeted PCR., Results: Four eyes of four patients (51 ± 8.8 years old) were evaluated. The main risk factors were soft contact lens wear (75%) and trauma with vegetative matter (50%). A superficial infiltrate was displayed in the majority of patients. Three cases (75%) showed hyphae on IVCM. All patients showed clinical improvement after topical antifungal therapy, although mostly through a combination of two antifungals (75%). One patient with a deeper infection required a systemic antifungal agent after one month of topical therapy. All cases required debridement to reduce the microbial load and enhance drug penetration. All patients experienced keratitis resolution following medical treatment (average: 3.3 months)., Conclusions: The identification of risk factors and the early diagnosis of Beauveria bassiana keratitis are fundamental in order to avoid its penetration in the deeper corneal stromal layers. Topical antifungal drugs, possibly accompanied by ulcer debridement, may be a successful treatment if instilled from the early phases of the disease.

Background: Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD., Methods: A comprehensive search was conducted using the PubMed database, employing the keywords "photobiomodulation" and "age-related macular degeneration." All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review., Results: The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials., Conclusions: Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain., (© 2023. The Author(s).)

Introduction: To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS., Methods: This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch's membrane (BM) breaks and large BM dehiscences., Results: Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7 years), 73 eyes of 46 patients (81 ± 7 years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3-16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a "petaloid-like" pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P < 0.001). Among the 73 subclinical AS cases, 71 were affected by late AMD (57 with macular neovascularization, 14 with geographic atrophy), showing a more advanced AMD stage in comparison with AMD eyes without subclinical AS (P < 0.001). The following OCT features were disclosed: BM breaks in 100% of cases and BM dehiscences in 37%., Conclusions: Subclinical AS in eyes with AMD is a peculiar phenotype of the disease, with features suggesting a primary involvement of Bruch's membrane and clinical similarities with mild, late-onset pseudoxanthoma elasticum., (© 2023. The Author(s).)

Competing Interests: E. Borrelli is a consultant/advisor for: AbbVie, Apellis, Bayer Shering-Pharma, Hoffmann-La-Roche, Zeiss. F. Bandello is a consultant for: AbbVie, Alimera Sciences, Bayer Shering-Pharma, Boehringer-Ingelheim, Fidia Sooft, Hoffmann-La-Roche, Novartis, NTC Pharma, Oxurion NV, SIFI. All other authors report no conflicts of interest.

Introduction: This study aimed to describe the effects of no-dose full-fluence photodynamic therapy without verteporfin (no-dose PDT) and to compare no-dose PDT with half-dose verteporfin full-fluence photodynamic therapy (HDFF PDT) for managing chronic central serous chorioretinopathy (cCSC)., Methods: This retrospective study evaluated 11 patients with chronic recurrent CSC treated with no-dose PDT between January 2019 and March 2022. Most of these patients were also treated with HDFF PDT a minimum of 3 months before and were considered as the control group. We described the changes of best corrected visual acuity (BCVA), maximum subretinal fluid (mSRF), foveal subretinal fluid (fSRF), and choroidal thickness (CT) 8 ± 2 weeks after no-dose PDT, and we compared BVCA, mSRF, fSRF, and CT of no-dose PDT with those of the of same patients previously treated with HDFF PDT., Results: Fifteen eyes of 11 patients (10 male, mean age 54 ± 12 years) received no-dose PDT; among these, 10 eyes of 8 patients (7 male, mean age 53 ± 12 years) also received HDFF PDT. Three eyes showed complete resolution of fSRF after no-dose PDT. No significant differences were disclosed between treatment with and without verteporfin comparing BCVA, mSRF, fSRF, and CT at baseline and 8 ± 2 weeks from the treatment (p > 0.05 in all analyses)., Conclusion: BVCA and CT significantly improved after no-dose PDT. Short-term functional and anatomical treatment outcomes for cCSC were similar for HDFF PDT and no-dose PDT. We hypothesize that the potential benefits of no-dose PDT may arise from thermal elevation that triggers and enhances photochemical activities by endogenous fluorophores, activating a biochemical cascade response that rescues/replaces sick, dysfunctional retinal pigment epithelial (RPE) cells. Results of this study suggest the potential value of a prospective clinical trial to evaluate no-dose PDT for managing cCSC, especially when verteporfin is contraindicated or unavailable., (© 2023. The Author(s).)

Purpose: To investigate retinal vessels functionality in patients with acute central serous chorioretinopathy (CSC) undergoing oral eplerenone or photodynamic therapy (PDT) using Retinal Vessel Analyzer (RVA) and Dynamic Vessel Analyzer (DVA), respectively., Methods: Treatment naïve acute CSC patients presenting between May 2017 and June 2017 were recruited. A complete ophthalmological examination was performed in all participants before and after oral eplerenone (eplerenone group) or half-dose PDT (PDT group)., Results: Eighteen eyes of 18 patients affected by acute CSC underwent either oral eplerenone (10 eyes of 10 patients, 47.6 ± 8.9 years old) or half-dose PDT (8 eyes of 8 patients, 57.4 ± 6.2 years old), respectively. After 2 months of treatment, non-significant variations of static retinal vessels analysis, dynamic arterial and venous dilatation were reported in eplerenone group. Similarly, in PDT group non-significant variations of static retinal vessels analysis, dynamic arterial and venous dilatation were found after 2 months of treatment., Conclusions: Static and dynamic retinal functionalities in acute CSC may not be significantly improved by oral eplerenone and half-dose PDT. Although their choroidal effects, these treatments could not exert a significant effect on retinal vessels motility. Thus, both local and systemic therapies might not help avoiding the onset of vascular and other retinal known alterations of CSC.

Purpose: To evaluate differences in acquisition time, peripheral extension, and chromaticity between 3 different commercialized ultra-wide-field (UWF) fundus cameras., Methods: Patients were prospectively enrolled from 07/2021 to 11/2021. Patients underwent fundus photography with the following scanning protocols: (1) single shot with Silverstone (Optos, California), two-shot montage with Clarus 500 (Carl Zeiss, Dublin, CA), and three-shot montage with iCare EIDON FA with UWF module (CenterVue Spa, a company of iCare Finland Oy; Vantaa, Finland). Acquisition time was calculated as the interval between the beginning and the end of the acquisition. Peripheral extension was quantified as the average ratio between the total retinal pixel area and the optic nerve head (ONH) pixel area. The average chromaticity of all pixels in the red-green-blue (RGB) space was calculated., Results: Twenty-three eyes of 13 prospectively enrolled healthy controls were included in the study. Optos Silverstone had a higher total retina area/ONH area ratio (509.1 [480.9;559.3]) compared to Zeiss Clarus (442.0 [431.9;510.5], p = 0.02) and iCare EIDON (369.7 [345.3;387.8], p < 0.0001). Silverstone demonstrated the shortest acquisition time (median [interquartile range]: 32 [20;58.5] s) compared to Zeiss Clarus (42 [28.5;53.5] s, p = 0.6733) and iCare EIDON (72 [68.5;78] s, p = 0.0003). iCare EIDON demonstrated the lowest variability of acquisition time (9.5 s), compared to Zeiss Clarus (25 s) and Optos Silverstone (38.5 s). A statistically significant difference was found in the RGB distribution between each of the 3 devices (p < 0.001). iCare EIDON demonstrated an average barycenter position (RGB = [0.412, 0.314, 0.275]) that represented the best color balance of the image. Zeiss Clarus had a noticeable red shift at the expense of the blue and green channels (RGB = [0.515, 0.294, 0.191]). Optos Silverstone showed an absence of the blue channel (RGB = [0.621, 0.372, 0.007]) which results in a distortion of the color of the image., Conclusion: Optos Silverstone and Zeiss Clarus required less time than iCare EIDON to acquire a comparable size image and captured larger areas of the retina than iCare EIDON. iCare EIDON provided more color-balanced retinal images with greater richness of color content than the other two devices., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To analyse the longitudinal changes in visual acuity and risk factors for recurrence or development of choroidal neovascularisation (CNV) in eyes with acute or chronic central serous chorioretinopathy (CSCR)., Methods: This was a retrospective, multicentric, longitudinal, observational study done in patients with a diagnosis of unilateral or bilateral CSCR and having at least 4 years of follow-up between the years 1999 and 2020. Kaplan-Meier curves were used for assessing cumulative risks. Multivariate logistic, linear and cox regression models were used for risk factor analyses. The trend in visual acuity, cumulative risks of recurrence and CNV formation was analysed., Results: A total of 117 out of 175 eyes (66.8%) had stable or improvement in vision at last follow-up, while 24 eyes had more than/equal to 3 line loss of vision. Four eyes (7.7%) with acute CSCR at initial presentation developed features of chronic CSCR at the final presentation. Thirty-seven eyes had recurrence during the follow-up with a 10-year cumulative recurrence rate of around 30%. On Cox proportional hazard regression analysis, history of previous treatment and male gender (p = 0.03) were associated with a lower risk of recurrence. Twenty-four developed de novo CNV by the end of follow-up and higher age (p = 0.001) and a higher number of recurrences (p = 0.05) were associated with a higher risk of early de novo CNV formation. The cumulative 10-year CNV development rate was 17.4%., Conclusion: A non-temporal relationship between acute and chronic CSCR was seen. Previous treatment, smoking and baseline RPE abnormality affected recurrence of SRF or CNV formation., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR)., Methods: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses., Results: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (β = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (β = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st-3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR., Conclusion: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early., (© 2023 S. Karger AG, Basel.)

Introduction: To analyze visual and anatomical outcomes after switch to intravitreal brolucizumab therapy in eyes affected by neovascular age-related macular degeneration (nAMD) previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents., Methods: Retrospective study of eyes with nAMD that underwent intravitreal brolucizumab at San Raffaele Hospital (Milan, Italy) or San Rocco Clinical Institute (Ome, Italy) between January 2021 and July 2022. All study eyes had persistent residual retinal fluid after receiving at least 3 intravitreal injections of other anti-VEGF agents prior to switch to brolucizumab., Results: Among 66 eyes from 60 patients (35 males; mean age 76.5 ± 7.4 years) with nAMD, 43 (65.2%) eyes received a complete loading dose of 3 brolucizumab injections, while 15 (22.7%) and 8 (12.1%) eyes were treated with 2 or 1 brolucizumab injections, respectively. The average number of brolucizumab injections was 2.5 during 4.0 ± 2.0 months (mean interval between two injections of 51.2 days). Lower letter gains (&lt;5 letter improvement from baseline) were found in eyes that did not complete a loading dose, after a greater number of previous anti-VEGF injections, after a longer duration of disease, and in eyes with a greater rate of macular atrophy at baseline. No serious ocular or systemic adverse events were found after switch to brolucizumab., Conclusion: nAMD eyes with persistent residual retinal fluid despite frequent anti-VEGF treatment can still gain functional and anatomical improvements after switch to brolucizumab therapy. Despite a relevant heterogeneity in patients' response to brolucizumab, we identified potential biomarkers for functional and anatomical improvement., (© 2023 S. Karger AG, Basel.)

Purpose: To investigate fellow eyes of newly diagnosed unilateral exudative Type 3 (T3) macular neovascularization (MNV) patients by assessing the presence and progression of a preclinical neovascular component during a 3-year follow-up., Methods: This is a longitudinal study involving three retinal referral centers. Patients affected by unilateral exudative treatment-naive T3 MNV were enrolled., Results: Twenty-four eyes of 24 patients (79 ± 6 years old) were enrolled. Nine eyes (37%) displayed a nonexudative T3 MNV at baseline that developed exudation after a mean of 9 ± 9 months. Fifteen eyes that did not display a nonexudative Type 3 MNV at baseline. Five eyes (21%) did not display neovessels at baseline, but showed a nonexudative T3 after 13 ± 9 months, and exudation after 8 ± 3 months. Five eyes (21%) developed active exudative T3 MNV after 23 ± 9 months, with no detectable nonexudative stage at baseline. Five eyes (21%) did not show MNV, but progressed to geographic atrophy by 36 months of follow-up. Overall, T3 MNV in the fellow eye accounted for 79%, all developing exudation over 3 years of follow-up., Conclusion: The occurrence of a nonexudative T3 MNV is a frequent event in the fellow eye of patients newly diagnosed with unilateral exudative T3 MNV and it precedes the development of exudation over 3 years (prevalence of 37% and cumulative incidence of 79%). Optical coherence tomography angiography approach may be used to perform an early diagnosis and treatment of patients with T3 MNV.

Purpose: To identify baseline OCT predictors of the 3-year visual outcome for type 3 (T3) macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) treated by anti-vascular endothelial growth factor (VEGF) therapy., Design: Retrospective longitudinal study., Participants: Forty eyes of 30 patients affected by exudative treatment-naive T3 MNV were enrolled., Methods: Baseline best-corrected visual acuity (BCVA) and several baseline OCT features were assessed and included in the analysis. Univariate and multivariate analyses served to identify risk factors associated with the 3-year BCVA., Main Outcome Measures: Baseline OCT features that are associated with bad or good visual outcomes of T3 MNV treated by anti-VEGF injections., Results: Mean baseline BCVA was 0.34 ± 0.28 logarithm of the minimum angle of resolution (LogMAR), which significantly decreased to 0.52 ± 0.37 LogMAR at the end of the 3-year follow-up (P = 0.002). In the univariate analysis, the following baseline features were associated with the 3-year BCVA outcome: baseline BCVA (P = 0.004), foveal involvement of exudation (P = 0.004), and presence of subretinal fluid (SRF; P = 0.004). In the multivariate model, baseline BCVA (P = 0.032), central macular thickness (P = 0.036), number of active T3 lesions (P = 0.034), and presence of SRF (P = 0.008) were associated with the 3-year BCVA outcome. Interestingly, 3-year BCVA was significantly lower in 19 eyes with SRF at the baseline (0.69 ± 0.42 LogMAR) than 21 eyes without SRF (0.37 ± 0.24 LogMAR; P = 0.004)., Conclusion: We identified structural OCT features associated with BCVA outcome after 3-year treatment with anti-VEGF injections. In contrast to previous studies on neovascular AMD, in our series, the presence of SRF at baseline was the most significant independent negative predictor of functional outcomes. Current findings may be employed to identify less favorable T3 patterns potentially deserving a more intensive treatment., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: Since its relevance on diagnosis and prognosis of diabetic retinopathy (DR), this review will examine a multimodal imaging approach to detect diabetic macular ischemia (DMI)., Methods: A PubMed engine search was carried out using the term "macular ischemia" paired with "diabetes," and "diabetic macular ischemia" paired to "fluorescein angiography," "ultra-wide field fluorescein angiography," "optical coherence tomography angiography," "octa," "2D octa," "ultra-wide field octa," "3D octa," "visual acuity." All studies published in English up to October 2021 irrespective of their publication status were reviewed, and relevant publications were included in this review., Results: Recently, new technologies have been proposed as an alternative to fluorescein angiography (FA), which is an actual diagnostic gold standard technique. Nowadays, optical coherence tomography angiography (OCTA) has emerged as the most promising and reliable procedure able to provide a qualitative and quantitative description of DMI. Newer three-dimensional (3D) OCTA approach will be discussed too. Moreover, we will discuss how OCTA might identify preclinical alterations before the onset of DR and allow prediction about the progression of disease., Conclusion: OCTA has significantly expanded our knowledge on diabetic macular ischemia., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Purpose: The purpose of this study was to investigate a confocal scanning laser ophthalmoscopy (cSLO) ultra-widefield (UWF) swept-source optical coherence tomography (S-SOCT) in assessment of diabetic choroidopathy and to evaluate the agreement of measurements with a spectral-domain OCT (SD-OCT) instrument., Methods: We conducted a cross-sectional study of patients with diabetes evaluating the choroidal vascularity index (CVI) in the nasal, temporal, and central macula segments of a UWF SS-OCT scan centered to the fovea. UWF pseudocolored fundus images were used for diabetic retinopathy (DR) severity staging. The CVI values were compared between different degrees of severity of DR and different posterior-pole sectors with linear mixed models. Central macula CVI measurements were repeated on SD-OCT scans; the interobserver intraclass coefficient (ICC) was calculated between SS-OCT and SD-OCT., Results: A total of 151 eyes of 85 patients were included. The CVI values decreased from nonproliferative DR to proliferative DR, with high-risk proliferative DR having significantly lower CVI values than moderate to severe nonproliferative DR (P = 0.03). The central macula region was the most evidently affected; the nasal sector was the least affected. The agreement between SS-OCT and SD-OCT was moderate (ICC = 0.50)., Conclusions: Diabetic choroidopathy progresses with worsening of DR toward proliferative disease; choroidal depletion is more prominent in the macula. Caution is recommended in comparing CVI values between different devices., Translational Relevance: Choroidal vascularity informs about the severity of DR and its complications, such as macular edema. The agreement between readers and between instruments may be suboptimal in certain cases.

To evaluate differences in macular and optic disc circulation in patients affected by Wolfram Syndrome (WS) employing optical coherence tomography-angiography (OCTA) imaging. In this retrospective study, 18 eyes from 10 WS patients, 16 eyes of 8 patients affected by type I diabetes and 17 eyes from 17 healthy controls were enrolled. All patients were imaged through OCT and OCTA and vascular parameters, as perfusion density (PD) and vessel length density (VLD) were measured. OCTA showed reduced PD in WS patients at the macular superficial capillary plexus (SCP, 27.8 ± 5.3%), deep vascular complex (DVC, 33.2 ± 1.9%) and optic nerve head (ONH, 21.2 ± 9.1%) compared to both diabetic patients (SCP 33.9 ± 1.9%, P < 0.0001; DVC 33.2 ± 0.7%, P = 1.0; ONH 33.9 ± 1.3, P < 0.0001) and healthy controls (SCP 31.6 ± 2.5, P = 0.002; DVC 34.0 ± 0.7%, P = 0.089; ONH 34.6 ± 0.8%, P < 0.0001). Similarly, VLD was lower in WS patients at the SCP (10.9 ± 2.7%) and ONH levels (7.5 ± 4.1%) compared to diabetic patients (SCP 13.8 ± 1.2%, P = 0.001; DVC 13.8 ± 0.2%, P < 0.0001; ONH 13.0 ± 0.7%, P =  < 0.0001), but higher in DVC (15.7 ± 1.2%, P < 0.0001). Furthermore, VLD was lower in WS patients in all the vascular parameters compared to controls (SCP 13.8 ± 1.5%, P < 0.0001; DVC 17.3 ± 0.6%, P < 0.0001; ONH 15.7 ± 0.5%, P < 0.0001). A significant microvasculature impairment in the macular SCP and ONH microvasculature was demonstrated in eyes affected by WS. Microvascular impairment may be considered a fundamental component of the neurodegenerative changes in WS., (© 2022. The Author(s).)

Purpose: To investigate the correlation between choroidal vascularity index and the enlargement of geographic atrophy (GA) lesion secondary to age-related macular degeneration during the 2-year follow-up., Methods: In this longitudinal observational study, 26 eyes (26 patients, mean age 75.7 ± 8.8 years) affected by GA were included. Choroidal vascularity index was calculated in the subfoveal 3000-µm area. The main outcome measure included correlation analysis between baseline choroidal vascularity index and the rate of GA enlargement., Results: During the 2-year follow-up, the mean GA area increased from 6.99 ± 5.28 mm2 to 10.69 ± 6.61 mm2(P < 0.001), accounting for a growth rate of 0.35 ± 0.20 and 0.31 ± 0.17 mm/year after the square root transformation in the first and second year of follow-up, respectively. Stromal choroidal area significantly decreased during the 2-year follow-up (P = 0.002). Interestingly, there was a significant correlation between the baseline choroidal vascularity index and the rate of GA enlargement (r=-0.432, P = 0.027) and between stromal choroidal area and the rate of GA enlargement (r = 0.422, P = 0.032). No other significant relationship was disclosed among choroidal parameters with the rate of GA enlargement., Conclusion: Choroidal vascularity index impairment is strictly related to the rate of GA enlargement during the 1-year and 2-year follow-up in patients affected by GA. For this reason, choroidal vascularity index could be considered a predictor of GA progression in the clinical setting, and it could be considered as a new potential biomarker in the efficacy evaluation of new GA interventions.