Vascular density normative data of radial peripapillary capillary plexus in healthy Caucasian subjects.

PURPOSE: To establish a normative database for vascular density (VD) of radial peripapillary capillary plexus (RPC) in healthy Caucasian subjects. METHODS: 633 healthy Caucasian subjects underwent a complete ophthalmological examination, including slit-lamp biomicroscopy, best corrected visual acuity measurement with Early Treatment Diabetic Retinopathy Study charts, intraocular pressure measurement, fundus examination, and macular and optic nerve head (ONH) structural optical coherence tomography (OCT). En-face 4.5 × 4.5 mm OCT angiography scans of the RPC plexus were recorded and VD values, automatically provided by the AngioAnalytics™ software, noted. We statistically estimated the impact of age and gender on RPC VD values using a linear mixed model. RESULTS: 560 subjects fully met inclusion criteria and, according to age, were stratified into 5 groups: 18-50 years (77), 51-60 years (160), 61-70 years (110), 71-80 years (132), and ≥ 81 years (81). Overall, mean RPC VD of the whole en-face image was 53.03 ± 4.27%. Age was significantly related to RPC VD values of whole en-face image (r = -0.454; p < 0.0001), which decreased with aging. The linear mixed model disclosed that age has a statistically significant effect on RPC VD values in whole en-face image (p = 0.0006). As age increases, RPC VD values decrease by 0.12 per year. Conversely, no significant gender-related differences were found in terms of RPC VD values of whole en-face image and each parapapillary quadrant analyzing all age group. CONCLUSIONS: Results show that RPC VD values in healthy Caucasian subjects decrease with aging. These data may be used to create a reference normative database useful for clinical use. KEY MESSAGES: What is known Radial peripapillary capillary (RPC) plexus, consisting of long parallel capillaries with rare bifurcations and anastomosis and extending straight along the course of the retinal nerve fiber layer to the posterior pole, may be affected early in some optic nerve head (ONH) and retinal diseases. What is new This study reports RPC vascular density (VD) values, automatically measured on optical coherence tomography angiography, in healthy Caucasian subjects, demonstrating that age is negatively related to RPC VD values. Results show that RPC VD values in healthy Caucasian subjects decrease with aging. These data may be used to create a reference normative database useful for clinical use.

Optical coherence tomography angiography macular biomarkers of peripheral retinal ischemia in diabetic macular edema: secondary endpoints from the clinical study "FOVEA".

PURPOSE: To investigate the relationship between the macular values of fractal dimension (FD) and lacunarity (LAC) on optical coherence tomography angiography (OCTA) images and the presence of peripheral retina non-perfusion areas (NPAs) on fluorescein angiography (FA) in patients with treatment-naïve diabetic macular edema (DME). METHODS: Fifty patients with treatment-naïve DME underwent a full ophthalmic examination, including best-corrected visual acuity measurement, FA, spectral-domain optical coherence tomography, and OCTA. Specifically, FA was performed to detect the presence of retinal NPAs, whereas fractal OCTA analysis was used to determine macular FD and LAC values at the level of the superficial and deep capillary plexus (SCP and DCP). FA montage frames of the posterior pole and peripheral retina, as well as macular OCTA slabs of the SCP and DCP, were obtained. RESULTS: Thirty (60%) eyes with FA evidence of peripheral retinal NPAs in at least one quadrant showed significantly lower FD and higher LAC in both SCP and DCP, when compared with eyes presenting a well-perfused peripheral retina. Furthermore, macular FD and LAC values were found to be significantly associated with the extent of retinal NPAs. CONCLUSIONS: Macular FD and LAC of both SCP and DCP seem to be strongly associated with the extent of peripheral retinal NPAs, thus suggesting that may be useful predictive biomarkers of peripheral ischemia in treatment-naïve DME eyes.

A large-scale screening identified in USH2A gene the P3272L founder pathogenic variant explaining familial Usher syndrome in Sardinia, Italy.

BACKGROUND: Usher syndrome (USH) encompasses a group of disorders characterized by congenital sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP). We described the clinical findings, natural history, and molecular analyses of USH patients identified during a large-scale screening to identify quantitative traits related to ocular disorders in the SardiNIA project cohort. METHODS: We identified 3 USH-affected families out of a cohort of 6,148 healthy subjects. 9 subjects presented a pathological phenotype, with SNHL and RP. All patients and their family members underwent a complete ophthalmic examination including best-corrected visual acuity, slit-lamp biomicroscopy, fundoscopy, fundus autofluorescence, spectral-domain optical coherence tomography, and electrophysiological testing. Audiological evaluation was performed with a clinical audiometer. Genotyping was performed using several arrays integrated with whole genome sequence data providing approximately 22 million markers equally distributed for each subject analyzed. Molecular diagnostics focused on analysis of the following candidate genes: MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. RESULTS: A single missense causal variant in USH2A gene was identified in homozygous status in all patients and in heterozygous status in unaffected parents. The presence of multiple homozygous patients with the same phenotypic severity of the syndromic form suggests that the Sardinian USH phenotype is the result of a founder effect on a specific pathogenic variant related haplotype. The frequency of heterozygotes in general Sardinian population is 1.89. Additionally, to provide new insights into the structure of usherin and the pathological mechanisms caused by small pathogenic in-frame variants, like p.Pro3272Leu, molecular dynamics simulations of native and mutant protein-protein and protein-ligand complexes were performed that predicted a destabilization of the protein with a decrease in the free energy change. CONCLUSIONS: Our results suggest that our approach is effective for the genetic diagnosis of USH. Based on the heterozygous frequency, targeted screening of this variant in the general population and in families at risk or with familial USH can be suggested. This can lead to more accurate molecular diagnosis, better genetic counseling, and improved molecular epidemiology data that are critical for future intervention plans. TRIAL REGISTRATION: We did not perform any health-related interventions for the participants.

Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia.

PURPOSE: To ascertain the prevalence and clinical and genetic features of age-related macular degeneration (AMD) in subjects living in the Lanusei valley, Central Sardinia, Italy, involved in a study on ageing (SardiNIA project). METHODS: A total of 814 volunteers aged ≥ 50 years, randomly selected from the SardiNIA project dataset, were included. A color fundus (CF) photograph of the 30° central retina of each eye was obtained and graded according to the Age-Related Eye Disease Study system. Life-style choices were investigated using standardized questionnaires. The concentrations of several inflammatory biomarkers (i.e., complement component, fibrinogen, and C-reactive protein) were measured. Polygenic risk score (PRS) was calculated and compared with results obtained from a European cohort. RESULTS: A total of 756 subjects had gradable CF photographs for AMD detection. In 91.3%, no signs of AMD were observed. The prevalence rates of early and late AMDs were 6.9% and 0.6%, respectively. A total of 85% of subjects were physically active; only 13.5% were current smokers. Low concentrations of complement component, fibrinogen, and C-reactive protein were found. We calculated the polygenic risk scores (PRS) using 40 AMD markers distributed on several candidate genes in Europeans and Sardinians. The mean PRS value was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectively, p = 1.18 × 10-77). CONCLUSIONS: In our cohort, most subjects showed no sign of any AMD type and late AMD was a condition rarely observed. Results of genetic, biochemical, and life-style investigation support the hypothesis that Sardinia population may present of a peculiar background with a protective effect against AMD development.

POLYPOIDAL CHOROIDAL NEOVASCULARIZATION VERSUS TYPE 1 CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION: A Fractal Analysis Study.

PURPOSE: To compare quantitative optical coherence tomography angiography parameters between polypoidal choroidal neovascularizations (PCNVs) and Type 1 choroidal neovascularizations (CNVs) in patients with age-related macular degeneration. METHODS: PCNV and Type 1 CNV lesions were retrospectively recruited in a cohort of patients with age-related macular degeneration. All the patients underwent a comprehensive ophthalmic evaluation, including best-corrected visual acuity, fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT), and optical coherence tomography angiography.Vascular perfusion density, fractal dimension, and lacunarity were computed by means of fractal analysis of neovascular en face optical coherence tomography angiography slabs. RESULTS: Sixty-eight eyes were included in the analysis. Of them, 35 of 68 eyes (51.5%) had PCNV and 33 of 68 (48.5%) had Type 1 CNV. Patients with PCNV were significantly younger (P = 0.0003) and had a higher best-corrected visual acuity (P < 0.0001). The mean vascular perfusion density was 0.83 ± 0.11% in PCNVs and 0.46 ± 0.10% in Type 1 CNVs (P < 0.0001). The mean fractal dimension was 1.44 ± 0.1 in PCNVs and 1.45 ± 0.09 in Type 1 CNVs (P = 0.86) while the mean lacunarity was 2.46 ± 1.03 in PCNVs and 1.86 ± 0.52 in Type 1 CNVs (P = 0.006). CONCLUSION: PCNVs resulted to be more heterogeneous and characterized by higher vascular perfusion density and lacunarity values than Type 1 CNVs. These interesting findings seem to support the idea that PCNVs and Type 1 CNVs are two separate clinical entities. However, future studies based on optical coherence tomography angiography fractal analysis, but also involving other relevant parameters such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions on whether PCNV is a specific clinical entity or a neovascular age-related macular degeneration variant.

Red Cell Distribution Width (RDW) and Complete Blood Cell Count-Derived Measures in Non-Arteritic Anterior Ischemic Optic Neuropathy.

Purpose: To assess the role of complete blood cell count (CBC) dimensional indices and CBC-derived measures in non-arteritic anterior ischemic optic neuropathy (NA-AION). Methods: In this retrospective case-control survey, 37 newly diagnosed NA-AION patients and 37 sex- and age-matched cataract controls were enrolled in 2017-2018. On the same day of NA-AION diagnosis, a blood sample was collected and CBC was determined using an automatic blood counter. CBC dimensional indices, such as mean platelet volume (MPV) and red cell distribution width (RDW), and CBC-combined indices, including neutrophil/lymphocyte ratio (NLR), derived NLR [dNLR = neutrophils/(white blood cells - neutrophils)], and platelet/lymphocyte ratio (PLR), were evaluated. Erythrocyte sedimentation rate (ESR) was also measured. Results: Mean platelet count, median MPV, RDW, NLR, and dNLR were 221±48 x 109/L, 8.2 fL (IQR=7.6-8.9), 13% (IQR=12-14.5), 2.50 (IQR=1.77-3.06), and 1.73 (IQR=1.31-2.07) in NA-AION patients and 248±56 x 109/L, 7.60 fL (IQR=7.05-8.25), 12% (IQR=11.6-13), 1.95 (IQR=1.43-2.49) and 1.36 (IQR=1.07-1.69) in controls. NA-AION patients showed significantly lower platelet count (p=0.03) and significantly higher median values of MPV (p=0.01), RDW (p=0.015), NLR (p=0.03), and dNLR (p=0.01). Multivariate logistic regression models disclosed a significant correlation only between higher levels of RDW and NA-AION (p≤0.05). The attributable risk of the association between NA-AION and RDW was 33%. Conclusions: Results suggest that RDW may be somehow involved in the pathogenesis of NA-AION. However, high-quality cohort studies are warranted to confirm whether, or not, an altered RDW may be considered a potential biomarker of this vascular disorder affecting the optic nerve.

QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF INACTIVE MACULAR NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare quantitative optical coherence tomography angiography parameters between treatment-naïve quiescent macular neovascularizations (MNVs) and previously treated nonexudative Type 1 MNVs, in patients with age-related macular degeneration. METHODS: The eyes included in the study were analyzed by fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. According to their medical history and multimodal imaging evaluation, Type 1 MNVs were divided into 2 groups: 1) treatment-naïve quiescent MNVs; 2) previously treated nonexudative Type 1 MNVs. Quantitative optical coherence tomography angiography parameters, including perfusion density (PD), fractal dimension (FD), and lacunarity (LAC) were calculated. Receiver operating characteristic curves, showing the ability of PD, FD, and LAC to discriminate between the two MNV groups, were built. RESULTS: Twenty-two eyes with treatment-naïve quiescent MNVs and 20 eyes with MNVs previously treated nonexudative Type 1 MNVs were analyzed. Mean FD and LAC were statistically different between the two study groups (P < 0.05). Lacunarity showed the best discrimination ability, followed by FD and PD (area under curve = 0.83, 0.78, 0.62, respectively). CONCLUSION: Results suggest that FD and LAC may be useful optical coherence tomography angiography biomarkers to objectively discriminate inactive MNVs with different prognosis, such as treatment-naïve quiescent MNVs and previously treated nonexudative Type 1 MNVs, in age-related macular degeneration patients.

PREDICTIVE ACTIVATION BIOMARKERS OF TREATMENT-NAIVE ASYMPTOMATIC CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the long-term evolution of treatment-naive quiescent choroidal neovascularization (CNV), in age-related macular degeneration (AMD), to identify predictive activation biomarkers. METHODS: Patients with quiescent CNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiographies, structural optical coherence tomography (OCT), and OCT angiography. Qualitative and quantitative analyses of structural OCT and OCT angiography images were performed during the study period. At the last follow-up evaluation, the enrolled eyes were divided into two groups: eyes with quiescent CNV converting to exudative AMD (eAMD) and those not progressing to eAMD. RESULTS: Sixty-eight eyes of 68 patients were enrolled in the study. Mean follow-up duration was 40 ± 28 months using multimodal imaging and 22 ± 13 months using OCT angiography. On structural OCT, quiescent CNV not converting to eAMD showed a preferential growth of the pigment epithelium detachment greatest linear diameter (P = 0.009), whereas the eAMD group presented a preferential growth of the pigment epithelium detachment maximal height (P < 0.0001) during the study period. Quantitative analysis of choriocapillaris OCT angiograms confirmed the CNV area growth during follow-up (from 4.18 ± 4.77 mm at baseline to 5.10 ± 5.06 mm at the last follow-up visit; P = 0.02). CONCLUSION: A close follow-up is recommended to early identify predictive activation biomarkers of treatment-naive quiescent CNV.

Novel mutations in c2orf71 causing an early onset form of cone-rod dystrophy: A molecular diagnosis after 20 years of clinical follow-up.

Purpose: Cone rod-dystrophies (CRDs) are pigmentary retinopathies mainly involving cones. CRDs typically present with decreased visual acuity and loss of sensitivity in the central visual field, reflecting the primary dysfunction of cones associated with night blindness and concentric visual field loss due to rod dysfunction. We describe the phenotype, natural history, and molecular analysis results of an early onset form of CRD. Methods: An otherwise healthy 25-year-old man from Sardinia, Italy, initially presented with subacute visual loss and central scotoma in both eyes. He underwent a complete ophthalmic examination, electrophysiologic testing, and genetic counseling. We first applied a candidate gene approach on ABCA4 to detect mutations; then, we performed exome sequencing (WES) on all family members to identify causative mutations. Results: The ophthalmic examination was unremarkable except the fundus examination, which revealed a well-circumscribed ring-shaped area of choroidal and RPE atrophy surrounding the fovea in the left eye and small white patches of atrophy around the fovea in the right eye. The ocular features and medical history were consistent with a diagnosis of CRD. Twenty years later, he showed a marked impairment in visual function, secondary to severe atrophic maculopathy associated with sparse pigmentary deposits. Molecular analysis identified two novel frameshift mutations in C2orf71: c.3039dupC: p.Ser1014Leufs*93 and c.1804_1805delAG:p. His603Argfs*77. Conclusions: The mutations in C2orf71 reported in this study comprise protein truncation mutations, which are likely to be involved in the pathogenesis of this severe form of early onset CRD.

EVALUATION OF PATCHY ATROPHY SECONDARY TO HIGH MYOPIA BY SEMIAUTOMATED SOFTWARE FOR FUNDUS AUTOFLUORESCENCE ANALYSIS.

PURPOSE: To evaluate the progression of patchy atrophy in high myopia using semiautomated software for fundus autofluorescence (FAF) analysis. METHODS: The medical records and multimodal imaging of 21 consecutive highly myopic patients with macular chorioretinal patchy atrophy (PA) were retrospectively analyzed. All patients underwent repeated fundus autofluorescence and spectral domain optical coherence tomography over at least 12 months. Color fundus photography was also performed in a subset of patients. Total atrophy area was measured on FAF images using Region Finder semiautomated software embedded in Spectralis (Heidelberg Engineering, Heidelberg, Germany) at baseline and during follow-up visits. Region Finder was compared with manually measured PA on FAF images. RESULTS: Twenty-two eyes of 21 patients (14 women, 7 men; mean age 62.8 + 13.0 years, range 32-84 years) were included. Mean PA area using Region Finder was 2.77 ± 2.91 SD mm at baseline, 3.12 ± 2.68 mm at Month 6, 3.43 ± 2.68 mm at Month 12, and 3.73 ± 2.74 mm at Month 18 (overall P < 0.005); this accounts for PA progression rate of 0.821 mm/year. Atrophy progression was significantly greater among eyes with larger PA compared with smaller baseline PA at Months 6, 12, and 18. There was no statistically significant difference between semiautomated Region Finder PA area and manually measured PA area on FAF images. CONCLUSION: Fundus autofluorescence analysis by Region Finder semiautomated software provides accurate measurements of lesion area and allows us to quantify the progression of PA in high myopia. In our series, PA enlarged significantly over at least 12 months, and its progression seemed to be related to the lesion size at baseline.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY VERSUS PHOTODYNAMIC THERAPY IN THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) compared with intravitreal vascular endothelial growth factor (VEGF) inhibitors alone or combined with PDT in the treatment of choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). METHODS: Retrospective study of a consecutive series of 34 white patients (34 eyes) with angiographic evidence of choroidal neovascularization secondary to chronic central serous chorioretinopathy, divided into two groups followed for at least 12 months: 16 were treated with full fluence PDT (PDT group) and 18 with vascular endothelial growth factor inhibitors (intravitreal [IVT] group). RESULTS: In the PDT group, mean best-corrected visual acuity (BCVA) was 20/40 (0.30 ± 0.69 logMAR) at baseline and did not change after 12 months (20/40; 0.30 ± 0.49 logMAR [P = 0.49]). In the IVT group mean, best-corrected visual acuity was 20/40 (0.30 ± 0.69 logMAR) at baseline and also did not change at the 12-month follow-up (20/32; 0.20 ± 0.49 logMAR [P = 0.20]). There was no statistically significant difference between the two groups in terms of best-corrected visual acuity. A statistical significance difference was found in central macular thickness between the two groups with a better reduction of the thickening in the PDT group (P = 0.05); moreover, indocyanine green angiography analysis revealed that 50% of the polypoidal lesions were closed after PDT and 25% of the polypoidal lesions disappeared after anti-vascular endothelial growth factor therapy at 12-month follow-up. CONCLUSION: PDT and IVT inhibitors alone or combined show similar clinical effects in chronic central serous chorioretinopathy eyes with choroidal neovascularization.

Efficacy and Safety of Fluocinolone Acetonide Implant in Diabetic Macular Edema: Practical Guidelines from Reference Center.

Diabetic macular edema (DME) is a common complication of diabetic retinopathy. Treatment with intravitreal injections is effective in most cases but is associated with a high therapeutic burden for patients. This implies the need for long-term treatments, such as the fluocinolone acetonide (FAc) implant. A review of basic science, pharmacology, and clinical data was conducted to provide a state-of-the-art view of the FAc implant in 2024. Although generally well tolerated, the FAc implant has been associated with ocular hypertension and cataract, and caution should be advised to the patients in this regard. By synthesizing information across these domains, a comprehensive evaluation can be attained, facilitating informed decision-making regarding the use of the FAc implant in the management of DME. The main objective of this review is to provide clinicians with guidelines on how to introduce and use the FAc implant in a patient with DME.

Ocular Tics and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).

Little is known about ocular tics in Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections (PANDAS). In this retrospective study, we examined the clinical records of children with motor tics referred to the Ophthalmology Unit, Azienda Ospedaliero-Universitaria di Sassari, Italy, in 2010-2019. The presence of ocular tics was investigated. Data about antistreptolysin O (ASO) and anti-DNase B antibody titers, erythrocyte sedimentation rate (ESR), plasma C-reactive protein (CRP), and antibiotic use were recorded. Forty children (thirty-four boys and six girls; mean age: 7.65 ± 2.5 years) with motor tics were identified; thirty-three (82.5%) showed ocular tics. Children with ocular tics had significantly higher titers of anti-DNase B antibodies (p = 0.04) and CRP (p = 0.016) than those with extraocular tics. A diagnosis of PANDAS was made in 24 (60%) children. PANDAS children with oculomotor tics had significantly higher titers of anti-DNase B antibodies (p = 0.05) than those with extraocular tics. Oral antibiotics were given to 25/33 (76%) children with ocular tics and 21/24 (87.5%) with PANDAS. All treated patients showed marked improvement/complete resolution of symptoms. Results suggest that higher titers of anti-DNase B antibodies may be implicated in the pathogenesis of ocular tics in PANDAS. Oral antibiotics may be beneficial in improving ocular tics. Further research is necessary to confirm our findings.

Combined Branch Retinal Artery and Central Retinal Vein Occlusion: A Systematic Review.

We performed a systematic review and analyzed the current available data on branch retinal artery occlusion (BRAO) with simultaneous central retinal vein obstruction (CRVO), a rarely described occurrence. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Studies were considered eligible if they (1) described patients with simultaneous BRAO + CRVO and (2) had been published in peer-reviewed journals. We initially identified 239 records from databases. Ultimately, only 19 reports met the selection criteria. Twenty-nine patients (15 men, 14 women; mean age 43 ± 15 years) were analyzed. Seventeen (59%) patients presented vascular risk factors. Mean visual acuity at onset and final visual outcome were 20/83 and 20/45, respectively, an insignificant improvement. Vision improved in 48% of cases. A marked heterogeneity in treatment approach was found. Eight (28%) patients received no therapy, whereas for 21 (72%) a large variety of topical and/or systemic drugs was given. In the treated group, mean visual acuity at onset and final visual outcome were 20/90 and 20/44, respectively, a not statistically significant improvement. Results suggest that combined BRAO + CRVO occurs at a younger age than isolated BRAO or CRVO. At present, there is insufficient evidence to support any specific management to improve vision in simultaneous BRAO + CRVO.

Intraocular Inflammation and Palpable Purpura in a Patient with Interstitial Pasteurella multocida Pneumonia.

PURPOSE: We describe a case of intraocular inflammation and palpable purpura in a patient with Pasteurella multocida pneumonia. METHODS: A 75-year-old pseudophakic woman with type-2 diabetes and chronic obstructive pulmonary disease complained of lower limb palpable purpura and right vision loss of five-day duration. On admission, right visual acuity was hand motion. Slit-lamp examination disclosed severe conjunctival and ciliary injection, corneal oedema, 3-mm hypopyon with heavy fibrin accumulation and blood clots, and synechiae to the IOL. RESULTS: Chest computed tomography revealed interstitial pneumonia. Sputum culture yielded P. multocida. Amoxicillin/clavulanic tablets (1 g × 3/daily) and topical and systemic steroids were given. Later on, fluorescein angiography showed multiple choroidal lesions bilaterally. With the above-mentioned therapy, there was full recovery of the skin, lung, and eye lesions. CONCLUSION: This report emphasizes that P. multocida infection should be considered in patients with intraocular inflammation, palpable purpura, and interstitial pneumonia. A multidisciplinary approach is necessary for a correct diagnosis and management.

Predictive Factors of Visual Outcome in Treatment-Naïve Diabetic Macular Edema: Preliminary Results from the Clinical Study "FOVEA".

Diabetic macular edema (DME) is a common cause of vision impairment in diabetic retinopathy. The aim of this study was to analyze the relationship between visual outcome and anatomic changes detected by traditional multimodal retinal imaging and optical coherence tomography angiography (OCTA) in DME eyes under treatment with Aflibercept. METHODS: Sixty-six DME eyes of 62 patients under treatment with intravitreal Aflibercept and with one-year follow-up were enrolled. All participants underwent a full ophthalmic evaluation, including best correct visual acuity (BCVA) measurement, spectral-domain optical coherence tomography, fluorescein angiography and OCTA, both at baseline and final examination. Fractal OCTA analysis of the superficial and deep capillary plexus (SCP and DCP) was performed to estimate vascular perfusion density and lacunarity (LAC). RESULTS: At the final examination, there was a significant improvement in terms of BCVA and central macular thickness (CMT). Furthermore, eyes with CMT <373 µm at baseline reached the higher BCVA at the last follow-up. Eyes with CMT ≥373 µm and DCP LAC <0.41 reached a higher final BCVA, if compared with eyes showing the same CMT but higher initial LAC. CONCLUSION: A 12-month treatment with intravitreal Aflibercept for DME resulted in significant visual and anatomic improvement. Multimodal retinal imaging, together with fractal OCTA analysis, may provide useful biomarkers, predictive of visual outcome in DME.

OCT Angiography Fractal Analysis of Choroidal Neovessels Secondary to Central Serous Chorioretinopathy, in a Caucasian Cohort.

Central serous chorioretinopathy (CSCR) can be complicated by different types of choroidal neovascularization (CNV). The purpose of this study was to investigate the incidence and quantitative optical coherence tomography angiography (OCT-A) features of CSCR-related CNVs. METHODS: This was a retrospective multicenter study including 102 eyes of 102 Caucasian patients with acute or complex CSCR. All patients underwent a comprehensive ophthalmological examination. Quantitative OCT-A parameters, including vascular perfusion density (VPD), fractal dimension (FD), and lacunarity (LAC), were measured in CNV eyes. RESULTS: Forty eyes (39.2%) had acute CSCR, whereas the remaining sixty-two (60.8%) had complex CSCR. CNV was observed in 37 (36.27%) eyes, all of which had the complex form. CNVs were classified as type 1 CNV in 11/37 (29.73%) cases and as polypoidal choroidal vasculopathy (PCV) in the remaining 26/37 (70.27%). Overall, the mean VPD, FD, and LAC of CSCR-related CNVs were 0.52 ± 0.20%, 1.44 ± 0.12, and 2.40 ± 1.1, respectively. No significant difference between type 1 CNV and PCV was found. CONCLUSION: Complex CSCR is often complicated by type 1 CNV and PCV with similar neovascular architecture and branching complexity, a finding supporting the idea that they might be different stages of the same neovascular process. Future OCT-A fractal analysis-based studies that also include other relevant parameters, such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions.

Evaluation of Radial Peripapillary Capillary Density in G6PD Deficiency: An OCT Angiography Pilot Study.

Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder causing hemolytic anemia. The purpose of this pilot study was to compare vascular density (VD) values of the radial peripapillary capillary (RPC) plexus in G6PD-deficient and G6PD-normal men, using optical coherence tomography angiography (OCTA). METHODS: 46 G6PD-deficient men and 23 age-matched male controls were included. A complete ophthalmological evaluation, consisting of slit-lamp biomicroscopy, best-corrected visual acuity, intra-ocular pressure measurement, structural optical coherence tomography, and OCTA scanning of the optic nerve head, was performed. The en-face angioflow images were carefully analyzed and the VD values of the RPC plexus were measured using the AngioAnalytics™ software embedded in the OCTA device. Medical conditions, including systemic hypertension, hypercholesterolemia, and diabetes mellitus, were also investigated. RESULTS: G6PD-deficient eyes showed higher values of VD in all peripapillary sectors, but a statistical significance (p = 0.03) was reached only in the infero-temporal sector. There were no significant differences in terms of hypercholesterolemia, systemic arterial hypertension, and diabetes mellitus between the two study groups. CONCLUSION: Results show that VD values of the RPC plexus are higher in G6PD-deficient men than in G6PD-normal subjects, but a statistically significant difference was found only in the inferior temporal sector. Overall, our preliminary findings support the hypothesis that the RPC layer of G6PD-deficient men consists of a denser vascular network, which may contribute to offering protection against ocular atherosclerotic vasculopathies.

Fractal analysis of polypoidal choroidal neovascularisation in age-related macular degeneration.

AIM: To describe optical coherence tomography angiography (OCTA) features of polypoidal choroidal neovascularisation (PCNV) secondary to age-related macular degeneration. METHODS: A retrospective consecutive series of 51 patients with a diagnosis of PCNV, based on clinical and multimodal imaging, was analysed. All patients with PCNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT) and OCTA. Two blinded retinal specialists carefully reviewed OCTA slabs in order to assess the morphological patterns of PCNV lesions. Furthermore, fractal analysis of PCNV en face images on OCTA, including vascular perfusion density (VPD), fractal dimension (FD) and lacunarity (LAC), was performed. RESULTS: Fifty-one PCNV eyes were included in the study. In all, the branching vascular network appeared hyper-reflective. Polyps showed two different patterns: in 34/51 (67%) eyes, they corresponded to hypo-reflective structures, whereas in the remaining 17 (33%) eyes, they appeared as hyper-reflective lesions. In all PCNV eyes, mean VPD, FD and LAC were 0.76±0.17%, 1.46±0.12 and 2.4±0.87, respectively. No significant difference was found between PCNVs showing a different OCTA pattern, in terms of quantitative OCTA parameters. CONCLUSION: Fractal analysis provides quantitative parameters demonstrating that PCNVs with different OCTA patterns share the same neovascular architecture and branching complexity. These new findings improve our ability to interpret OCTA slabs, opening new areas of discussion about this type of neovascular lesion.