RP1 Dominant p.Ser740* Pathogenic Variant in 20 Knowingly Unrelated Families Affected by Rod-Cone Dystrophy: Potential Founder Effect in Western Sicily.

Background and Objectives. Retinitis pigmentosa (RP) is the most common inherited rod-cone dystrophy (RCD), resulting in nyctalopia, progressive visual field, and visual acuity decay in the late stages. The autosomal dominant form (ADRP) accounts for about 20% of RPs. Among the over 30 genes found to date related to ADRP, RP1 pathogenic variants have been identified in 5-10% of cases. In a cohort of RCD patients from the Palermo province on the island of Sicily, we identified a prevalent nonsense variant in RP1, which was associated with ADRP. The objective of our study was to analyse the clinical and molecular data of this patient cohort and to evaluate the potential presence of a founder effect. Materials and Methods. From 2005 to January 2023, 84 probands originating from Western Sicily (Italy) with a diagnosis of RCD or RP and their relatives underwent deep phenotyping, which was performed in various Italian clinical institutions. Molecular characterisation of patients and familial segregation of pathogenic variants were carried out in different laboratories using Sanger and/or next-generation sequencing (NGS). Results. Among 84 probands with RCD/RP, we found 28 heterozygotes for the RP1 variant c.2219C>G, p.Ser740* ((NM_006269.2)*, which was therefore significantly prevalent in this patient cohort. After a careful interview process, we ascertained that some of these patients shared the same pedigree. Therefore, we were ultimately able to define 20 independent family groups with no traceable consanguinity. Lastly, analysis of clinical data showed, in our patients, that the p.Ser740* nonsense variant was often associated with a late-onset and relatively mild phenotype. Conclusions. The high prevalence of the p.Ser740* variant in ADRP patients from Western Sicily suggests the presence of a founder effect, which has useful implications for the molecular diagnosis of RCD in patients coming from this Italian region. This variant can be primarily searched for in RP-affected subjects displaying compatible modes of transmission and phenotypes, with an advantage in terms of the required costs and time for analysis. Moreover, given its high prevalence, the RP1 p.Ser740* variant could represent a potential candidate for the development of therapeutic strategies based on gene editing or translational read-through therapy for suppression of nonsense variants.

Choroidal Thickness and brolucizumab intravitreal injection: Cause or effect of intraocular inflammation?

PURPOSE: to analyze the structural changes of choroidal thickness in patients with brolucizumab-related exudative vitritis after intravitreal injection, using EDI-OCT. METHODS: One hundred eyes of one hundred patients, affected by exudative age related-macular degeneration treated with brolucizumab intravitreal injection between January 2022 and august 2023 at Eye clinic of University of Federico II Naples, were enrolled. All eyes underwent macular examination using Enhanced Deep Imaging-OCT (Spectralis, Heidelberg Engineering inc.) preoperatively and at each postoperative check (1, 3, 6, 12 months). Anterior segment evaluation at slit lamp before and after injection was performed. RESULTS: Of the 100 treated eyes, 4 showed inflammatory signs related to exudative vitreitis, with inflammation signs at slit lamp examination and confirmed by OCT and B scan ecography. EDI-OCT revealed, in all of these 4 patients, a significant increase of choroidal thickness compared to baseline. CONCLUSION: choroidal thickness could be correlated in the inflammatory response generated in patients undergoing treatment with brolucizumab.

Optical coherence tomography angiography features in Waldenström macroglobulinemia patients without Hyperviscosity syndrome: a pilot prospective study.

PURPOSE: To evaluate the retinal vessel density (VD) with optical coherence tomography angiography (OCTA) in in asymptomatic patients affected by Waldenström macroglobulinemia (WM) without hyperviscosity syndrome (HVS) and to highlight the presence of microvascular damage in theese clinically asymptomatic WD patients. DESIGN: Prospective study. METHODS: A total of 43 eyes from 43 WM patients (24 females, 19 males, mean age 55.1 ± 13.6 years) were enrolled from January 2023 to December 2023 in the Eye Clinic of the University of Naples Federico II. .Along with WM patients, 40 healthy subjects (HS) (20 females, 20 males, mean age 52.3 ± 15.6 years) with a normal ophthalmic examination and no history of intraocular surgery or retinal pathologic features were included as control group All patients and controls underwent OCTA RESULTS: The two groups were not significantly different for age and sex Visual acuity examination showed no statistically significant difference in BCVA between controls and patients Compared to HS, WD patients showed lower VD values in the SCP in the whole image (47.95 ± 5.17% vs. 52.99 ± 2.52%; p < 0.001), as well as in the parafovea (53.01 ± 6.69% vs. 55.30 ± 2.61%; p = 0.002), and fovea (21.38 ± 9.01% vs. 30.31 ± 5.84%; p < 0.0001). On the other hand, in the DCP VD values were significantly higher in patients compared to controls in the whole image (55.82 ± 8.07% vs. 50.83 ± 5.46%; p = 0.005), as well as in the parafovea (56.76 ± 6.26% vs. 52.59 ± 5.46%; p = 0.0001), and fovea (38.75 ± 8.59% vs. 33.43 ± 8.68%; p < 0.0001). CONCLUSION: The finding that OCTA confirmed the presence of widespread microvascular damage in WD patients clinically silent. Thus, OCTA is a safe rapid imaging technique that could represent a valid biomarker of systemic vascular dysfunction.

Evaluation of changes in epivascular glia before and after intravitreal dexamethasone implant: An OCT pilot study.

PURPOSE: To detect changes in epivascular glia (EVG) in diabetic retinopathy after intravitreal dexamethasone implant using en face optical coherence tomography (enface OCT) and OCT angiography (OCTA) and to correlate improvements in functional and structural features. METHODS: A total of 38 eyes of 38 patients were enroled in this prospective study. They were divided into two different study groups: the first group including 20 eyes with diabetic retinopathy type 1 complicated by macular oedema and the control group including 18 eyes from 18 healthy age-matched patients. The main outcome measures were: (i) differences at baseline in the foveal avascuar zone (FAZ) area in the study group versus control; (ii) the presence of epivascular glia in the study group versus control, (iii) differences at baseline between foveal macular thickness versus control; (iv) changes in foveal macular thickness, FAZ and epivascular glia in the study group before and after intravitreal dexamethasone implant. RESULTS: At baseline FAZ area detected at OCTA was larger in the study group than in the control group, and epivascular glia was only detected in the study group. Three months after intravitreal injection of dexamethasone implant in the study group the best corrected visual acuity (BCVA) improved and central macular tickness reduced (P<0.0001). No significant differences were found in FAZ area while epivascular glia disappeared in 80% of the patients after treatment. CONCLUSIONS: Glia activation due to retinal inflammation in diabetic retinopathy (DR) can be detected on en face-OCT as epivascular glia. Intravitreal dexamethasone (DEX) implant improves both the anatomical and functional condition in the presence of these signs.

Study of choroidal vasculature in open angle glaucoma patients.

PURPOSE: To investigate the vessel density (VD) of the choriocapillary (CC) plexus in patients affected by preperimetric glaucoma (PPG), advanced glaucoma (AG) and in a healthy control group using Optical Coherence Tomography Angiography (OCTA) in order to clarify the pathogenetic mechanisms of this disease. METHODS: In this prospective observational study, 19 eyes from 19 patients affected by preperimetric glaucoma (PPG) and 18 eyes from 18 patients affected by advanced glaucoma were studied from January 2022 to May 2022 at the University of Naples "Federico II". These patients had been compared with 20 eyes of 20 healthy subjects that represented the control group. All subjects underwent EDI-OCT to assess the subfoveal choroidal thickness (SFCT). OCTA was used to evaluate the vessel density (VD) of the CC in whole image in the studies groups. RESULTS: The PPG and AG groups showed a statistically significant reduction in CC vessel density parameters with respect to controls (p < 0.001). Regarding EDI OCT results AG patients exhibited a statistically significant increase in the SFCT compared to healthy controls (p < 0.001). Whereas,no statistically significant difference was between the PPG groups and to healthy controls (p 0.851). CONCLUSIONS: CC vessel density could represent a helpful and sensible biomarker to identify early choroidal microvascular changes in PPG and MCI in order to better understand the vascular pathophysiological mechanisms involved in glaucoma diseases.