Inner retinal layers' alterations of the microvasculature in early stages of Parkinson's disease: a cross sectional study.

PURPOSE: To investigate microcirculation characteristics of the inner retinal layers at the macula and the peripapillary area using Optical Coherence Tomography Angiography (OCT-A) of patients in early stages of Parkinson's disease (PD). METHODS: 32 PD patients and 46 age- and gender-matched healthy controls were included in this cross sectional study. OCT-A imaging was performed to analyze microcirculation characteristics at each separate macular region (fovea, parafovea, and perifovea) and the peripapillary area of the inner retinal layers. RESULTS: Individuals with PD had significantly lower parafoveal, perifoveal and total vessel density (VD) in the superficial capillary plexus (SCP) than controls (all p < 0.001), while foveal VD was higher in PD eyes than that of controls, though not statistically significant. Similarly, individuals with PD had significantly lower parafoveal, perifoveal and total perfusion in the SCP than control eyes (all p < 0.001), while foveal perfusion was significantly higher in PD eyes than that of controls (p = 0.008). PD eyes had significantly smaller FAZ area and perimeter accompanied by decreased circularity at the SCP as compared to controls (all p < 0.001). Concerning the peripapillary area, individuals with PD had significantly lower radial peripapillary capillary perfusion density and flux index at the SCP than controls (all p < 0.001). All p values remained statistically significant even after using the Bonferroni correction for multiple comparisons, except for that of foveal perfusion. CONCLUSIONS: Our study indicates alterations of the inner retinal layers at the macula and the peripapillary area at the preliminary stages of PD. OCT-A parameters could potentially comprise imaging biomarkers for PD screening and improve the diagnostic algorithms.

The large Hellenic Study of Uveitis: epidemiology, etiologic factors and classification.

PURPOSE: To analyse the demography, etiology, and classification of uveitis at a tertiary academic referral center. METHODS: An observational study was conducted on the archives of uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology at the University Hospital of Ioannina (Greece) from 1991 to 2020. This study aimed to investigate the epidemiological profile of patients, including their demographics and the main etiologic factors of uveitis. RESULTS: Out of 6191 cases with uveitis, 1925 were infectious, 4125 were non-infectious, and an overall of 141 masquerade syndromes were recorded. Among these cases, 5950 patients were adults, with a slight female predominance, while 241 were children (< 18 years old). Interestingly, 24.2% of cases (1500 patients) were associated with 4 specific microorganisms. Herpetic uveitis (HSV-1 and VZV/HZV) was the most common cause of infectious uveitis (14.87%), followed by toxoplasmosis (6.6%) and tuberculosis (2.74%). In 49.2% of non-infectious uveitis cases, no systematic correlation was found. The most frequent causes of non-infectious uveitis included sarcoidosis, white dot syndromes, ankylosing spondylitis, lens-induced uveitis, Adamantiades-Behçet disease, and idiopathic juvenile arthritis. Infectious uveitis was more common in the rural population, whereas non-infectious uveitis was more frequently recorded in the urban population CONCLUSIONS: Although our study was conducted on a predominantly white Caucasian population, it also reflects the effect of increasing immigration, improvements of diagnostic techniques, changes in referral patterns, and various actual changes in disease incidence.

Evaluation of the choriocapillaris after photodynamic therapy for chronic central serous chorioretinopathy. A review of optical coherence tomography angiography (OCT-A) studies.

PURPOSE: Emerging evidence suggests that choroidal microcirculation and microstructural changes after verteporfin photodynamic therapy (vPDT) for chronic central serous chorioretinopathy (CSC) can be shown in detail using OCT-Angiography (OCT-A). The use of OCT-A for the examination of choriocapillaris (CC) has attracted significant attention as the technique offers potential explanations for the effects of vPDT on choroidal tissue. METHODS: A meticulous literature search was performed in the PubMed database without restriction on year of publication until June 2021. The reference list of all electronically retrieved articles was carefully reviewed for potentially relevant articles that had not been identified. RESULTS: We identified and reviewed 11 studies reporting a comprehensive update on microvasculature and morphologic changes of the CC layer as seen on OCT-A in chronic CSC. The reviewed articles extensively analyze both the qualitative and quantitative characteristics of the CC flow pattern after applying vPDT safety-enhanced protocols. The changes in the CC plexus indicate the potential of beneficial or deleterious treatment effect on choroidal tissue remodeling. The reviewed series have revealed variability of flow pattern, vessel density, and perfusion of the CC over time. CONCLUSION: The CC plexus alterations during the post-vPDT period in chronic CSC may imply the treatment effect on choroidal tissue, indicating the potential of anatomical or functional recovery over time. The reviewed literature may confirm the diagnostic value of OCT-A in the assessment of the pathophysiology of eyes with CSC.

Vitreous inflammatory and angiogenic factors on patients with proliferative diabetic retinopathy or diabetic macular edema: the role of Lipocalin2.

PURPOSE: Quantitative analysis of vitreous inflammatory and angiogenic factors from patients with proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). MATERIALS AND METHODS: Collection of undiluted vitreous samples from 20 diabetic patients: 13 with proliferative diabetic retinopathy (PDR) and 7 with diabetic macular edema (DME). DME patients had suboptimal response to anti-VEGF treatment. Samples from 11 control patients, with vitreomacular interface pathology such as idiopathic epiretinal membrane (iERM) (n = 4), vitreomacular traction syndrome (VMT) (n = 3) and full thickness macular hole (FTMH) (n = 3), were also collected. The levels of IL1b, IL6, IL8, IL27, TNFα, ICAM-1, VCAM, MCP-1, VEGFA and LCN2 were measured using cytometry flow analysis. Median values were compared with Mann-Whitney test since the distributions were skewed. Statistical analysis was performed with the Statistical Package for Social Sciences software (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). RESULTS: The median concentration of LCN2, IL6, IL8, IL1b, IL27, ICAM, VCAM-1, MCP-1, TNFa and VEGFA was higher in PDR patients than in controls. Similarly, the median concentration of LCN2, IL6, IL8, IL27, ICAM, VCAM-1, TNFa and VEGFA was higher in DME patients than in controls. In particular, median LCN2 concentration in diabetic patients was 5,711 pg/ml (interquartile range [IR] = 2,534), while in controls was 2,586 pg/ml (IR = 2,345). Moreover, median LCN2 was 6,534 pg/ml in the DME group (IR = 6,850) and 4,785 pg/ml in the PDR group (IR = 2,608), (p = 0.025). CONCLUSION: Various inflammatory and angiogenic factors are involved in the pathophysiology of PDR and DME. Elevated vitreous levels of LCN2 in PDR and especially in DME patients reveal a potential pathogenic association. More extended studies could verify LCN2 as an alternative therapeutic target.

Retinal microcirculation characteristics in obstructive sleep apnea/hypopnea syndrome evaluated by OCT-angiography: a literature review.

PURPOSE: The retina may provide a window to estimate systemic vascular status; therefore, there has been interest in identifying microcirculation characteristics that possibly reflect hypoxic alterations in obstructive sleep apnea/hypopnea syndrome (OSAS). Emerging evidence has suggested that retinal microvasculature investigation holds the potential to characterize the pathophysiology involved in ocular manifestations of OSAS. The advent of optical coherence tomography angiography (OCT-A) has attracted significant attention as this technique offers detailed analysis of the retinal capillary plexus. METHODS: A detailed literature search was performed in PubMed database until December 2021. We identified and reviewed all papers referring to the alterations of the retinal capillary plexus in OSAS using OCT-A. RESULTS: A comprehensive update indicates that microcirculation alterations of the retinal capillary plexus utilizing OCT-A may differ with severity of OSAS and imply the potential underlying pathophysiology of ocular manifestations. The reviewed series have revealed variability concerning microvasculature characteristics at the macular and the peripapillary area. Further studies are warranted to establish the OCT-A parameters as biomarkers regarding the evaluation of OSAS in clinical practice. CONCLUSION: Retinal capillary plexus characteristics as seen on OCT-A reflect microvasculature alterations, potentially leading to concomitant ocular comorbidity in the context of OSAS. The reviewed literature may confirm the diagnostic and prognostic value of OCT-A in the assessment of the pathophysiology of ocular manifestations in OSAS and highlight unmet needs to be addressed by future research.

The contribution of multifocal visual evoked potentials in patients with optic neuritis and multiple sclerosis: a review.

PURPOSE: To review the evidence on the usefulness of the multifocal visual evoked potential (mfVEP) test in patients with optic neuritis (ON) and/or multiple sclerosis (MS). METHODS: We critically review key published evidence on the use of mfVEP in ON/MS patients and its association with other functional and structural tests. RESULTS: Multifocal VEP tests are useful in detecting abnormality in patients with ON/MS and monitor the progression of lesions (remyelination, atrophy). In addition, mfVEP has good correlation with conventional visual evoked potential (VEP), standard automated perimetry, optical coherence tomography and magnetic resonance imaging. In patients with ON, mfVEP might be useful in predicting the risk of conversion to MS.

Association of OCT-A characteristics with postoperative visual acuity after rhegmatogenous retinal detachment surgery: a review of the literature.

PURPOSE: Emerging evidence has suggested that macular microcirculation and microstructural changes after rhegmatogenous retinal detachment (RRD) successful reattachment surgery are currently evaluated in detail by OCT-Angiography (OCT-A). New imaging technology has revealed the existence of microscopic macular changes, even in cases that retinal morphology appears to be normal in fundus biomicroscopy. The use of OCT-A for the examination of foveal characteristics has attracted significant attention in recent years as the technique offers a potential explanation of the suboptimal recovery of visual acuity and incomplete restoration of the macula despite anatomical repair. However, the available evidence that is needed to establish the OCT-A parameters as predicting factors in clinical practice is both limited and contradictory. METHODS: A detailed review of the literature was conducted. The association of OCT-A characteristics with postoperative visual acuity after RRD surgery, including vitrectomy with gas tamponade and in some cases scleral buckle, was extensively analyzed. RESULTS: A comprehensive update on microcirculation and microstructural changes of the macula using OCT-A after RRD repair may indicate potential factors of functional outcomes in clinical practice. CONCLUSION: A review of the existing literature sheds light on the microvascular changes of the macular capillary plexus that may significantly affect functional outcomes after RRD surgery. The current article discusses important aspects of key publications on the topic, highlights the importance of long-term effectiveness of these possible prognostic factors and proposes the need for further future research.

Spirochetal uveitis: Spectrum of clinical manifestations, diagnostic and therapeutic approach, final outcome and epidemiological data.

PURPOSE: Analysis of cases with spirochetal uveitis related to spirochetes in a tertiary referral academic center. METHODS: Retrospective study of patients diagnosed with uveitis attributed to Treponema pallidum, Leptospira spp. and Borrelia burgdorferi from June 1991 until December 2019. RESULTS: A total of 57 cases of spirochetal uveitis (22 patients with T. pallidum, 26 with Leptospira spp., and 9 with B. burgdorferi) that consisted 1% of the overall number of uveitics were recorded. All these cases presented with a wide spectrum of clinical presentations (anterior uveitis, posterior uveitis, panuveitis, vasculitis, papillitis, and in some rare cases concomitant posterior scleritis). The treatment included mainly penicillin or doxycycline, while corticosteroids were administered systematically in some cases with Borrelia or Leptospira infection. The final visual outcome was favorable (> 6/10 in Snellen visual acuity) in approximately 76% of our patients. CONCLUSION: Despite being rare, spirochetal uveitis can be detrimental for the vision and must always be included in the differential diagnosis.

Bartonella henselae- and quintana-associated uveitis: a case series and approach of a potentially severe disease with a broad spectrum of ocular manifestations.

PURPOSE: To evaluate the clinical manifestations of intraocular inflammation associated with Bartonella infection and describe the assessment and management of patients with cat-scratch disease (CSD). METHODS: This is a retrospective review of the clinical records of patients diagnosed with Bartonella henselae and Bartonella quintana intraocular inflammation from 2011 to 2018 in the Department of Ocular Inflammations and Infections of the University Eye Clinic of Ioannina (Greece). An analysis of the current literature concerning Bartonella-related intraocular infections was also carried out. RESULTS: This is a retrospective study of 13 patients (7 males and 6 females) with a mean age of 39.2 years that were diagnosed with unilateral intraocular inflammation, except one case with bilateral affection, attributed to Bartonella (either henselae or quintana). Twelve (12) patients (92.3%) had a positive history of traumatic cat contact. The main ocular clinical findings with regard to the type of uveitis included neuroretinitis in 5 eyes (38.5%), vasculitis in 3 eyes (23.1%), iridocyclitis in 2 eyes (15.4%), intermediate uveitis in 2 eyes (15.4%), posterior uveitis in 1 eye (7.7%), panuveitis in 2 eyes (15.4%), retinochoroiditis in 2 eyes (15.4%), vitritis in 1 eye (7.7%), peripheral choroidal granuloma in 1 eye (7.7%). Immunoglobulin (Ig) G was positive in all cases. All patients were treated with antibiotics (mainly rifampicin, doxycycline and azithromycin). The visual acuity was noted to be improved in all patients after treatment, but some of them experienced disturbing complications. CONCLUSION: CSD may manifest with various ocular pathological findings. Taking into consideration the increasing frequency of infections by B. henselae and B. quintana, clinicians should always incorporate CSD in the differential diagnosis of such presentations of uveitis. Educating vulnerable groups (children, immunosuppressed, etc.) and also general population, the appropriate preventing measures can contribute in limiting the risk of infection.

Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility.

Hereditary retinal degenerations encompass a group of genetic diseases characterized by extreme clinical variability. Following next-generation sequencing and autozygome-based screening of patients presenting with a peculiar, recessive form of cone-dominated retinopathy, we identified five homozygous variants [p.(Asp594fs), p.(Gln117*), p.(Met712fs), p.(Ile756Phe), and p.(Glu543Lys)] in the polyglutamylase-encoding gene TTLL5, in eight patients from six families. The two male patients carrying truncating TTLL5 variants also displayed a substantial reduction in sperm motility and infertility, whereas those carrying missense changes were fertile. Defects in this polyglutamylase in humans have recently been associated with cone photoreceptor dystrophy, while mouse models carrying truncating mutations in the same gene also display reduced fertility in male animals. We examined the expression levels of TTLL5 in various human tissues and determined that this gene has multiple viable isoforms, being highly expressed in testis and retina. In addition, antibodies against TTLL5 stained the basal body of photoreceptor cells in rat and the centrosome of the spermatozoon flagellum in humans, suggesting a common mechanism of action in these two cell types. Taken together, our data indicate that mutations in TTLL5 delineate a novel, allele-specific syndrome causing defects in two as yet pathogenically unrelated functions, reproduction and vision.

Development of novel LOXL1 genotyping method and evaluation of LOXL1, APOE and MTHFR polymorphisms in exfoliation syndrome/glaucoma in a Greek population.

PURPOSE: In the Greek population of Epirus, exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) occur at a high prevalence. In this study, we validate a novel lysyl oxidase-like 1 (LOXL1) genotyping method, investigate the previously reported association of LOXL1 with XFS/XFG, and evaluate apolipoprotein E (APOE) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms as genetic risk factors for both conditions in our population. METHODS: Blood samples were collected from 82 patients with XFG, 69 patients with XFS, 52 patients with primary open-angle glaucoma (POAG), and 107 controls. APOE and MTHFR 677C>T genotyping was performed from extracted genomic DNA with established methods. A novel methodology of real-time PCR and melting curve analysis was developed and validated to accurately genotype the LOXL1 G153D and R141L polymorphisms by using two different fluorescent channels of the LightCycler instrument (Roche) examining each SNP separately. RESULTS: No significant differences were observed for the APOE and MTHFR polymorphisms between the patients with XFS, the patients with XFG, and the control subjects. The APOE ε2 allele appears to be associated with elevated risk of POAG in our population. Our novel LOXL1 genotyping method was easy to perform, fast, and accurate. A statistically significant association was found for the LOXL1 gene with XFS/XFG in this Greek population. The association of XFS and XFG with G153D appeared to be less powerful in this population (XFS: odds ratio [OR]=2.162, p=0.039, XFG: OR=2.794, p=0.002) compared to other populations, and for R141L, the association was proven only with XFG (OR=3.592, p<0.001). Neither of the two LOXL1 SNPs was significantly associated with POAG. CONCLUSIONS: We confirmed the association between LOXL1 and XFS/XFG, but the APOE and MTHFR polymorphisms are not significant risk factors for the development of XFS/XFG in our population of patients from Epirus (Greece).

Assessment of Maternal Retinal Microvasculature in Preterm Pregnancy Using OCT-Angiography: a Cross-Sectional Study.

Background: Pregnancy induces a cascade of hemodynamic changes that are likely to affect the maternal systemic and ocular circulation. Objective:The current study aimed to investigate retinal microvasculature alterations in women with preterm and full-term pregnancy using optical coherence tomography angiography (OCT-A). Design:This was a cross-sectional, comparative, single-center study. Methods:The present study included 21 women with preterm pregnancy, who were in the early postpartum period, and 18 controls with full-term pregnancy. Optical coherence tomography angiography imaging was performed to analyze macular microvasculature characteristics at the retinal superficial capillary plexus (SCP) and the choriocapillaris (CC). Results:In females with preterm pregnancy, the mean values of vessel density (VD) at the SCP of the total macular area were significantly higher than those in females with full-term pregnancy (p=0.001), and the mean values of foveal, parafoveal and perifoveal VD at the SCP were higher, though not statistically significant. Similarly, the mean values of perfusion at the SCP of the total macular area were significantly higher in females with preterm pregnancy than controls (p=0.023), while the mean values of foveal, parafoveal and perifoveal perfusion were higher, though not statistically significant. The mean values of foveal avascular zone (FAZ) parameters (area, perimeter, circularity) at the SCP in females with preterm pregnancy did not have any significant differences from those of controls. Concerning the measurements of choroidal parameters, there were no statistically significant differences in subfoveal choroidal thickness, as well as the CC OCT-A characteristics between females with preterm and full-term pregnancy. Conclusions:Our study indicates that retinal blood flow alterations may be present in the early postpartum period in women with preterm pregnancy. Increased macular vasculature may reflect the systemic perfusion changes compensating for placental insufficiency.

The Large Hellenic Study of Uveitis: Diagnostic and Therapeutic Algorithms, Complications, and Final Outcome.

PURPOSE: The purpose of this study is to present the diagnostic and therapeutic algorithms, complications, and final outcome in the management of uveitic patients at a tertiary academic referral center. DESIGN: Observational study. METHODS: Analysis of the archives of 6191 uveitic patients at the Ocular Inflammation Service of the Department of Ophthalmology of the University Hospital of Ioannina in Greece from 1991 to 2020. RESULTS: During the 30 years of the study, the diagnostic ability climbed from 45.43% (1991-1995) to 73.4% (2016-2020). This improvement was linked to several factors including the increase in the number of diagnostic paracenteses for the analysis of intraocular fluids, the range and quality of laboratory blood tests, the multimodal ophthalmic imaging, the proper use of nonophthalmic imaging, and the multidisciplinary approach. The degree of uveitis-related complications was related to the severity and cause of inflammation, the recurrence rate, inappropriate treatment, and the prolonged or initially inactive inflammation. The 3 most common complications included cataract, macular edema, and glaucoma. Apart from the modern treatments and surgical techniques, the 3-month preoperative control of inflammation played a critical role in the surgical outcomes. The percentage of patients with a successful outcome increased from 72% (2001-2005) to 90.50% (2016-2020). The center's experience, prompt referral, patient's compliance, and regular follow-ups are associated with a better outcome. The analysis of the results allowed the development of diagnostic and therapeutic algorithms. CONCLUSIONS: Developing diagnostic and therapeutic algorithms allows for the efficient management of uveitis, leading to better visual outcome and therefore a better quality of life.

Effect of silicone oil on retinal microcirculation after vitrectomy for rhegmatogenous retinal detachment evaluated by OCT angiography: a literature review.

Silicone oil (SO) has been widely used as intravitreal tamponade agent for rhegmatogenous retinal detachment (RRD) and has been occasionally associated with incomplete retinal structural and functional recovery. The use of Optical Coherence Tomography Angiography (OCT-A) has recently attracted significant attention for detailed analysis of retinal capillary plexus and blood flow changes as predicting factors for postoperative outcomes. A detailed literature search was performed in PubMed database until October 2022. The following keywords were used: rhegmatogenous retinal detachment, silicone oil, optical coherence tomography angiography, macular microvasculature, peripapillary capillary plexus, vessel density, and foveal avascular zone. We identified and reviewed 19 studies referring to microcirculation alterations of the retinal capillary plexus as seen on OCT-A in eyes treated by vitrectomy with intravitreal SO for RRD. A comprehensive update revealed variability of microcirculation characteristics of the retinal capillary plexus including the macular and the peripapillary capillaries. Further studies are warranted to clarify the OCT-A values in an attempt to identify the potential effect of SO on retinal tissue in clinical practice. A review of the existing literature sheds light on the effect of SO on retinal capillary plexus and the potential impact on functional outcomes after vitrectomy for RRD. This article discusses important aspects of key publications on the topic, highlights the importance to identify distinct alterations of the microvasculature status, and proposes the need for further future research in this field.

Long-Term Outcomes following Intravitreal Ranibizumab for Choroidal Neovascularization Related to Nd:YAG Laser Macular Injury: A Case Report.

Choroidal neovascularization (CNV) secondary to Nd:YAG laser macular injury consists of a rare condition without standardized treatment. Herein, we present the long-term outcomes of a case with a spontaneous closure of a laser-associated macular hole that was followed by late-onset CNV and was successfully treated with intravitreal ranibizumab. A 32-year-old man suffered a macula injury in his right eye after accidental exposure to an 800-nm wave length Nd:YAG laser pulse. Ophthalmological examination demonstrated deterioration in visual acuity along with parafoveal and post-hyaloid hemorrhage. After 1 month, fundoscopy indicated the formation of a full-thickness macular hole. A close observation revealed spontaneous closure of the hole and visual improvement within the next month. One and a half year later, the patient presented with sudden visual distortion, while optical coherence tomography and fluorescein angiography disclosed the development of CNV. The patient was successfully treated with a single intravitreal injection of ranibizumab. The patient's condition has remained stable during an 8-year follow-up period. In conclusion, laser-induced macular injury consists of an increasingly remarkable condition that may have a profound impact on visual outcomes. Our case provides insight into the potential mechanisms of Nd:YAG laser injury and its complications, indicating that CNV may occur even in the long term, while anti-vascular endothelial growth factor may help maintain stable anatomic and functional outcomes.

Macular microcirculation changes after macula-off rhegmatogenous retinal detachment repair with silicone oil tamponade evaluated by OCT-A: preliminary results.

Background: Rhegmatogenous retinal detachment (RRD) with macular involvement is a sight-threatening condition. Silicone oil (SO) is efficacious for retinal tamponade, especially in complex cases. Whether macular detachment per se or the potential tamponading agent may affect macular microcirculation after RRD repair is a matter of research. Objectives: To investigate macular microcirculation changes using optical coherence tomography angiography (OCT-A) after pars plana vitrectomy (PPV) with intravitreal SO for RRD repair in the early posttreatment period. Design: Prospective comparative cross-sectional study. Data sources and Methods: Fourteen eyes of 14 patients were included in the study. All eyes underwent a single successful PPV with SO tamponade for macula-off RRD. OCT-A was performed to analyze macular microcirculation and visual outcomes at 1 month postoperatively. The fellow unaffected eye was used as control. Results: Vessel density (VD) in the superficial capillary plexus (SCP) was significantly lower at each macular region (fovea, parafovea, and perifovea) of SO-treated eyes compared with the fellow eyes (all p = 0.001). Similarly, perfusion density (PD) in the SCP was significantly lower at each macular region than the fellow eyes (all p = 0.001). There was enlargement of foveal avascular zone (FAZ) area and decrease of circularity at RRD eyes compared with the fellow ones (all p = 0.001). Postoperative logMAR visual acuity (VA) was significantly lower in treated eyes than fellow eyes and correlated inversely with foveal, parafoveal, and perifoveal VD and PD SCP (all p < 0.001). Postoperative VA had no correlation with FAZ parameters. Conclusion: Enlargement of FAZ SCP and decrease in VD and PD SCP during the short-term follow-up were possibly attributable to ischemic changes in the macular area after RRD repair with SO tamponade. In this preliminary study, the flow density in macular capillary plexus may represent an indicator of visual outcomes.

Macular microcirculation characteristics in Parkinson's disease evaluated by OCT-Angiography: a literature review.

PURPOSE: Given the fact that retina may provide a window into the central nervous system, there has been interest in identifying retinal biomarkers as predicting factors of pathological processes in neurodegenerative disorders. Emerging evidence has suggested that macular microcirculation changes in Parkinson disease (PD) may indicate the alterations of cerebral microvasculature. The use of Optical Coherence Tomography Angiography (OCT-A) has attracted significant attention in recent years as this technique offers a detailed analysis of the existence of changes at the macular capillary plexus. METHODS: A detailed review of the literature was performed in PubMed until June 2021. We identified all papers referring to the alterations of the macular capillary plexus in PD using OCT-A. RESULTS: A comprehensive update indicates that microvasculature alterations of the macular capillary plexus utilizing OCT-A may comprise useful biomarkers regarding the cerebral vasculature in PD. Since the available evidence is limited, additional studies are warranted to establish the OCT-A parameters as predicting factors in clinical practice. CONCLUSIONS: A review of the existing literature sheds light on the microvasculature changes of the macular capillary plexus as seen on OCT-A in PD patients. The current article discusses notable aspects of key publications on the topic, highlights the importance of the potential long-term effectiveness of OCT-A biomarkers in PD and proposes the need for further future research.

The Choroid after Half-Dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

PURPOSE: To characterize choroidal structure and vasculature after half-dose verteporfin photodynamic therapy (hd-vPDT) in eyes with chronic central serous chorioretinopathy using Enhanced Depth Imaging Optical Coherence Tomography (EDI OCT) and Optical Coherence Tomography Angiography (OCT-A). METHODS: This prospective case-control study included 10 eyes. Choroid was examined before and at 1 month following hd-vPDT. We measured choroidal thickness (CT) at subfoveal area and at 750 µm nasal and temporal of fovea and thickness of Haller and choriocapillaris/Sattler layers. Whole (WA), luminal (LA) and interstitial area (IA) at EDI-OCT, and perfusion density at OCT-A were analyzed. The unaffected fellow eyes were used for comparisons. RESULTS: Mean CT at subfoveal area and at 750 µm nasal and temporal of fovea, values of Haller and choriocapillaris/Sattler layers and those of WA, LA and IA were reduced, while PD increased at 1 month after hd-vPDT (all p < 0.001). There was a significant (p < 0.05) negative correlation (ρ = -0.658) between PD and post-treatment logMARVA. None of analyzed parameters reached values of unaffected fellow eye. CONCLUSION: Following hd-vPDT, choroidal thickness with both luminal and interstitial components markedly decreased, while perfusion of choriocapillaris improved.

A Narrative Review of the Ocular Manifestations in Noonan Syndrome.

PURPOSE: The purpose of this review is to provide an update on ophthalmological manifestations of Noonan Syndrome (NS). Emerging evidence has suggested that NS patients may present with a wide spectrum of ocular characteristics. Detailed investigation of genotype has revealed the diversity of related gene mutations. The potential association of genetic basis with clinical expressivity of phenotype remains a challenging aspect of this issue. METHODS: A literature search was performed in PubMed; we have analyzed prospective and retrospective cohort studies, case reports, and reference lists of retrieved articles until February 2021. We identified all papers referring to NS ocular manifestations referring to genotype and phenotype characteristics. RESULTS: A comprehensive update on ocular manifestations of NS patients indicates significant evidence for variability of genotype and phenotype features. Ophthalmologic features of NS are characterized by a wide spectrum of abnormalities; external ocular malformations, distortions of refraction, alignment, motilily, anterior and posterior ocular segment and visual impairment. Currently, a variety of pathogenic mutations in patients with NS have been investigated, while the nature of the genetic variants may determine expressivity. Albeit it remains a clinical diagnosis with variation in the progress of each NS phenotype. Although the available evidence that is needed to establish genotype-phenotype correlation as predicting factor in clinical practice is limited, it could aid risk assessment and patient management. CONCLUSION: A review of the existing literature sheds light on the ocular characteristics of NS. The current article discusses notable aspects of key publications on the topic, highlights the importance of the potential genotype-phenotype correlation in clinical practice, and proposes the need for further future research.

Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype.

The aim of this study was to investigate coenzyme Q10 (CoQ10) biosynthesis pathway defects in inherited retinal dystrophy. Individuals affected by inherited retinal dystrophy (IRD) underwent exome or genome sequencing for molecular diagnosis of their condition. Following negative IRD gene panel analysis, patients carrying biallelic variants in CoQ10 biosynthesis pathway genes were identified. Clinical data were collected from the medical records. Haplotypes harbouring the same missense variant were characterised from family genome sequencing (GS) data and direct Sanger sequencing. Candidate splice variants were characterised using Oxford Nanopore Technologies single molecule sequencing. The CoQ10 status of the human plasma was determined in some of the study patients. 13 individuals from 12 unrelated families harboured candidate pathogenic genotypes in the genes: PDSS1, COQ2, COQ4 and COQ5. The PDSS1 variant c.589 A > G was identified in three affected individuals from three unrelated families on a possible ancestral haplotype. Three variants (PDSS1 c.468-25 A > G, PDSS1 c.722-2 A > G, COQ5 c.682-7 T > G) were shown to lead to cryptic splicing. 6 affected individuals were diagnosed with non-syndromic retinitis pigmentosa and 7 had additional clinical findings. This study provides evidence of CoQ10 biosynthesis pathway gene defects leading to non-syndromic retinitis pigmentosa in some cases. Intronic variants outside of the canonical splice-sites represent an important cause of disease. RT-PCR nanopore sequencing is effective in characterising these splice defects.