Predict and Protect: Evaluating the Double-Layer Sign in Age-Related Macular Degeneration.

INTRODUCTION: Advanced age-related macular degeneration (AMD) is a major cause of vision loss. Therefore, there is interest in precursor lesions that may predict or prevent the onset of advanced AMD. One such lesion is a shallow separation of the retinal pigment epithelium (RPE) and Bruch's membrane (BM), which is described by various terms, including double-layer sign (DLS). METHODS: In this article, we aim to examine and clarify the different terms referring to shallow separation of the RPE and BM. We also review current evidence on the outcomes associated with DLS: firstly, whether DLS is predictive of exudative neovascular AMD; and secondly, whether DLS has potential protective properties against geographic atrophy. RESULTS: The range of terms used to describe a shallow separation of the RPE and BM reflects that DLS can present with different characteristics. While vascularised DLS appears to protect against atrophy but can progress to exudation, non-vascularised DLS is associated with an increased risk of atrophy. Optical coherence tomography (OCT) angiography (OCTA) is the principal method for identifying and differentiating various forms of DLS. If OCTA is unavailable or not practically possible, simplified classification of DLS as thick or thin, using OCT, enables the likelihood of vascularisation to be approximated. Research is ongoing to automate DLS detection by applying deep-learning algorithms to OCT scans. CONCLUSIONS: The term DLS remains applicable for describing shallow separation of the RPE and BM. Detection and classification of this feature provides valuable information regarding the risk of progression to advanced AMD. However, the appearance of DLS and its value in predicting AMD progression can vary between patients. With further research, individualised risks can be confirmed to inform appropriate treatment.

Age-related macular degeneration (AMD) is an eye disease that may develop in older people, usually those aged over 60 years. Early in the disease, people often do not show any symptoms, but as the disease progresses, vision loss may occur. The advanced forms of AMD are called neovascular AMD (also called "wet" AMD) and advanced dry AMD (called geographic atrophy; GA). It is important to identify features and signs on eye scans that can help to predict if someone with AMD will develop an advanced form of the disease because this will help doctors plan the most appropriate treatment. One such feature on eye scans is the double-layer sign (DLS). In this article, we summarise the different names used for DLS, and assess if having a DLS increases the likelihood of someone with early AMD developing wet AMD or GA. We conclude that how DLS looks varies between people, which leads to DLS being called by various names. Someone with early AMD and a DLS containing blood vessels may be more likely to develop wet AMD; whereas someone with early AMD and a DLS without blood vessels may be more likely to develop GA. Taking photos of the eye using optical coherence tomography angiography imaging is the main method of identifying DLS and confirming whether it contains blood vessels.

Elderly Patient With Bilateral Central Serous Chorioretinopathy Misdiagnosed as Bilateral Wet Age-Related Macular Degeneration: A Case Report.

This report presents a unique case of a 77-year-old diabetic male patient with bilateral central serous chorioretinopathy (CSCR), who was receiving multiple bilateral intravitreal injections for a presumed diagnosis of wet age-related macular degeneration (AMD). The fundus examination did not show any signs of AMD or diabetic retinopathy (DR). The spectral domain optical coherence tomography (OCT) revealed bilateral subretinal fluid. The neovascular membrane was not visible on OCT angiography. Fundus fluorescein angiography (FFA) confirmed the absence of choroidal neovascularization (CNV). Notably, this represents a unique case of an elderly patient with CSCR mimicking occult CNV.

Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 2-year results from the Japan subgroup of the phase III TENAYA trial.

PURPOSE: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD). METHODS: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-naïve patients aged ≥ 50 years with nAMD were randomised (1:1) to intravitreal faricimab (6.0 mg up to every 16 weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0 mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N = 133) and global pooled TENAYA/LUCERNE cohort (N = 1329). RESULTS: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2 years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2. CONCLUSION: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections.

Subretinal hyperreflective material in retinal and chorioretinal disorders: A comprehensive review.

Subretinal hyperreflective material (SHRM) is a common and remarkable optical coherence tomography (OCT) biomarker whose importance is emerging in several retinal and chorioretinal diseases, including age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, pathologic myopia, posterior uveitis, vitelliform lesions and macular dystrophies, and rarer disorders. Multimodal imaging, also thanks to the introduction of OCT angiography, allowed a deeper characterisation of SHRM components and its morphological changes after treatment, suggesting its usefulness in clinical practice. We discuss and summarize the nature, multimodal imaging characteristics, and prognostic and predictive significance of SHRM in the different retinal and choroidal disorders in which it has been described.

Central Serous Chorioretinopathy. A Review.

Central serous chorioretinopathy (CSC) is a disease characterized by serous detachment of the neuroretina, especially in the posterior pole of the eye. It is often accompanied by serous detachment of the retinal pigment epithelium (RPE) and associated with the leakage of fluid into the subretinal space through the defective RPE. CSC most often affects men of working age. The exact pathophysiology of the disease is not completely known. Based on indocyanine green angiography (ICG), which revealed increased permeability of choroidal vessels, and optical coherence tomography (OCT) showing increased choroidal thickness, choroidal vasculopathy is assumed to be the primary cause of CSC. In most cases, CSC has a good prognosis with spontaneous resorption of the subretinal fluid (SRF) and improvement of visual functions. However, in a small percentage of patients the disease progresses to a chronic or recurrent course, and can lead to irreversible functional and anatomical changes of the retina with a final clinical picture of diffuse retinal pigment epitheliopathy (DRPE). The optimal treatment approach for patients with CSC remains controversial. In recent decades, myriad therapeutic approaches have been used in the treatment of chronic forms of CSC (cCSC); these included for example laser photocoagulation, pharmaceutical treatment, standard photodynamic therapy (PDT) or anti-VEGF. In recent years a less destructive method, specifically PDT in reduced dose regimens, either with a reduced dose of verteporfin or the laser beam energy used, has been preferred in the treatment of cCSC. Comparable efficacy and safety has been demonstrated using reduced-dose or reduced-fluence PDT regimens in patients with cCSC, with an improvement in best-corrected visual acuity and reduction of SRF.

CNV-Net: Segmentation, Classification and Activity Score Measurement of Choroidal Neovascularization (CNV) Using Optical Coherence Tomography Angiography (OCTA).

This paper aims to present an artificial intelligence-based algorithm for the automated segmentation of Choroidal Neovascularization (CNV) areas and to identify the presence or absence of CNV activity criteria (branching, peripheral arcade, dark halo, shape, loop and anastomoses) in OCTA images. Methods: This retrospective and cross-sectional study includes 130 OCTA images from 101 patients with treatment-naïve CNV. At baseline, OCTA volumes of 6 × 6 mm2 were obtained to develop an AI-based algorithm to evaluate the CNV activity based on five activity criteria, including tiny branching vessels, anastomoses and loops, peripheral arcades, and perilesional hypointense halos. The proposed algorithm comprises two steps. The first block includes the pre-processing and segmentation of CNVs in OCTA images using a modified U-Net network. The second block consists of five binary classification networks, each implemented with various models from scratch, and using transfer learning from pre-trained networks. Results: The proposed segmentation network yielded an averaged Dice coefficient of 0.86. The individual classifiers corresponding to the five activity criteria (branch, peripheral arcade, dark halo, shape, loop, and anastomoses) showed accuracies of 0.84, 0.81, 0.86, 0.85, and 0.82, respectively. The AI-based algorithm potentially allows the reliable detection and segmentation of CNV from OCTA alone, without the need for imaging with contrast agents. The evaluation of the activity criteria in CNV lesions obtains acceptable results, and this algorithm could enable the objective, repeatable assessment of CNV features.

[Photodynamic therapy in Germany-Quo vadis?] / Photodynamische Therapie in Deutschland ­ Quo vadis?

BACKGROUND: Photodynamic therapy (PDT) was originally approved for the treatment of neovascular age-related macular degeneration (nAMD) and secondary choroidal neovascularization in myopia (mCNV). In addition, it is used as an off-label treatment in patients with choroidal hemangioma, polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). OBJECTIVE: To track the development of PDT treatment numbers in Germany between 2006 and 2021 and to investigate the composition of the therapeutic indications. METHODS: In this retrospective study the quality reports of German hospitals were evaluated in the period from 2006 to 2019 and the number of PDTs performed was recorded. In addition, the range of indications for PDT was determined exemplarily for the Eye Center at Medical Center, University of Freiburg and the Eye Center at St. Franziskus Hospital in Münster between 2006 and 2021. Finally, the estimated prevalence of CSC and an estimate of cases requiring treatment were used to calculate the number of patients in need of PDT treatment in Germany. RESULTS: The number of PDTs performed in Germany decreased from 1072 in 2006 to 202 in 2019. While PDT was used in 86% of cases in patients with nAMD and in 7% of cases with mCNV in 2006, it was mainly performed in patients with CSC (70%) and choroidal hemangiomas (21%) from 2016 to 2021. With an estimated incidence of CSC of 1:10,000 and assuming that 16% of patients develop chronic CCS requiring treatment, approximately 1330 PDTs would need to be performed per year in Germany for patients with newly diagnosed chronic CSC alone. CONCLUSION: The decreasing numbers of PDT treatment performed in Germany is mainly due to a change to intravitreal injections as the preferred treatment for nAMD and mCNV. As PDT is currently the recommended treatment of choice for chronic CSC, an underprovision of PDT in Germany can be assumed. To enable an appropriate treatment for patients, a reliable verteporfin production, a simplified approval process by health insurance companies and a close cooperation between ophthalmologists in private practice and larger centers are urgently needed.

Biomarcadores de OCT-angiografía en la neovascularización coroidea tipo1 tras tratamiento con aflibercept durante 1 año / OCT angiography biomarkers in type1 choroidal neovascularisation after one year of aflibercept treatment

Objetivos: Evaluar la actividad de los biomarcadores, mediante OCT-angiografía (OCTA), en la neovascularización coroidea (NVC) secundaria a degeneración macular asociada a la edad (DMAE) tratada con aflibercept. Como objetivos secundarios se estudiaron la agudeza visual (AV) y la relación existente entre biomarcadores y pronóstico visual. Material y métodos: Estudio prospectivo en el que se estudiaron 33 ojos de 40 pacientes naïve diagnosticados de NVC tipo1 secundaria a DMAE y que habían sido tratados con aflibercept, según ficha técnica, durante 1año. Los pacientes fueron evaluados en el momento del diagnóstico, a los 4, a los 8 y a los 12meses. Resultados: La ganancia media de AV a los 12meses fue de 15,2±3,3 letras. El área de lesión disminuyó 1,2±1,0mm2 en el cuarto mes (p<0,0001), permaneciendo estable después. La presencia de capilares finos, anastomosis y halo hipointenso perilesional se redujo en el 85, el 70 y el 25%, respectivamente, a los 12meses de seguimiento. La arcada vascular periférica cambió de morfología, pasando de tener un aspecto frondoso a tener un aspecto afilado en el 90% de los casos. El tamaño de la lesión y la presencia/ausencia de halo hipointenso perilesional se asociaron, de manera independiente, a la AV final, de tal forma que las lesiones de mayor tamaño y la ausencia de halo hipointenso perilesional en la visita basal se asociaron a menor ganancia de AV. Conclusiones: La OCTA se trata de una herramienta útil, no invasiva, que nos aporta información cuantitativa y cualitativa del remodelado de la red vascular de la NVC tras terapia antiangiogénica. (AU)

Objective: To assess the activity of biomarkers, through OCT angiography (OCTA), of choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) treated with aflibercept. As secondary endpoints, visual acuity (VA) and the relationship between biomarkers and visual prognosis were also studied. Material and methods: Prospective study that examined 33 eyes of 40 naïve patients with type1 CNV secondary to AMD, who had been treated with aflibercept, according to summary of product characteristics, for one year. The patients were evaluated at the time of diagnosis, and at 4, 8 and 12months. Results: The mean VA gain at 12months was 15.2±3.3 letters. The area of lesion decreased 1.2±1.0mm2 in the 4th month (P<.0001), remaining stable afterwards. The presence of tiny capillaries, anastomosis and perilesional hypointense halo was reduced by 85%, 70% and 25%, respectively, at 12 months of follow-up. The peripheral vascular arcade changed morphology, from having a leafy appearance to having a sharp appearance in 90% of cases. The size of the lesion and the presence/absence of perilesional hypointense halo were independently associated with the final VA, in such a way that larger lesions and the absence of a perilesional hypointense halo at the baseline visit were associated with less VA gain. Conclusions: The OCTA is a useful, non-invasive tool that provides quantitative and qualitative information on the remodelling of the CNV vascular network after antiangiogenic therapy. (AU)

Potential CRISPR Base Editing Therapeutic Options in a Sorsby Fundus Dystrophy Patient.

TIMP3 mutations are associated with early-onset macular choroidal neovascularisation for which no treatment currently exists. CRISPR base editing, with its ability to irreversibly correct point mutations by chemical modification of nucleobases at DNA level, may be a therapeutic option. We report a bioinformatic analysis of potential therapeutic options in a patient presenting with Sorsby fundus dystrophy. Genetic testing in a 35-year-old gentleman with bilateral macular choroidal neovascularisation revealed the patient to be heterozygous for a TIMP3 variant c.610A>T, p.(Ser204Cys). Using a glycosylase base editor (GBE), another DNA-edit could be introduced that would revert the variant back to wild-type on amino acid level. Alternatively, the mutated residue could be changed to another amino acid that would be better tolerated, and for that, an available 'NG'-PAM site was found to be available for the SpCas9-based adenine base editor (ABE) that would introduce p.(Ser204Arg). In silico analyses predicted this variant to be non-pathogenic; however, a bystander edit, p.Ile205Thr, would be introduced. This case report highlights the importance of considering genetic testing in young patients with choroidal neovascularisation, particularly within the context of a strong family history of presumed wet age-related macular degeneration, and describes potential therapeutic options.

Central posterior hyaloidal fibrosis - A novel optical coherence tomography feature associated with choroidal neovascular membrane.

Purpose: To describe a novel optical coherence tomography (OCT) finding at the vitreomacular interface (VMI), and report its association with advanced choroidal neovascularisation (CNV). Observations: Optical coherence tomography (OCT) scans performed at three retinal imaging centres at Amanat Eye Hospital, Pakistan from May 2016 till May 2021 were reviewed. A specific change at the vitreomacular interface was noted consisting of abnormal hyper reflectivity at the point of attachment of the posterior hyaloid membrane to the foveal center which appears to 'fill in' the foveolar depression.Eight eyes of eight patients were identified. All affected eyes had advanced CNV and persistent vitreofoveolar adhesion. In all eyes, the foveal contour (concavity) was maintained and there was no inner retinal surface wrinkling which differentiates this OCT feature from vitreomacular traction or epiretinal membranes. The authors propose the term Central Posterior Hyaloidal Fibrosis (CPHF) for this specific OCT finding. Conclusions and Importance: Central Posterior Hyaloidal Fibrosis (CPHF) is a newly reported OCT finding associated with advanced CNV, which may represent a possible profibrotic influence of a choroidal neovascular membrane to the overlying posterior hyaloid adhesion.

Seeing through the cracks.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder showing phenotypic heterogeneity giving rise to complex comorbidities. The most 'visible' signs are dermatological; however, these may be subtle and hidden from the view of an affected individual. Ophthalmic signs can be easily missed, and here we highlight the importance of a multisystem assessment. We report a patient who developed advanced sight loss due to maculopathy whose underlying PXE aetiology went unnoticed until subtle skin signs were noticed on the lateral aspect of his neck. He was aware of the skin changes. Careful review of his previous retinal imaging showed the presence of 'angioid streaks' and anatomic alteration at the outer retina-Bruch membrane associated with his prior history of choroidal neovascularisation. The diagnosis was subsequently confirmed by skin biopsy and genetic testing. This case highlights the subtlety of both dermatological and ophthalmic signs in PXE.

Matrix Metalloproteinase 10 Contributes to Choroidal Neovascularisation.

Age-related macular degeneration (AMD) is currently the main cause of severe visual loss among older adults in developed countries. The pathophysiology has not been clarified, but oxidative stress is believed to play a major role. Matrix metalloproteinases (MMP) may play a prominent role in several steps of the pathophysiology of AMD, especially in its neovascular form; therefore, there is of great interest in understanding their role in choroidal neovascularisation. This study aimed to elucidate the role of MMP10 in the development of choroidal neovascularisation (CNV). We have demonstrated that MMP10 was expressed by retinal pigment epithelium cells and endothelial cells of the neovascular membrane, in cell culture, mouse and human retina. MMP10 expression and activity increased under oxidative stress conditions in ARPE-19 cells. MMP10-/- mice developed smaller laser-induced areas of CNV. Furthermore, to exclude a systemic MMP10 imbalance in these patients, plasma MMP10 concentrations were assessed in an age- and sex-matched sample of 52 control patients and 52 patients with neovascular AMD and no significant differences were found between the groups, demonstrating that MMP10 induction is a local phenomenon. Our findings suggest that MMP10 participates in the development of choroidal neovascularisation and promotes MMP10 as a possible new therapeutic target.

The role of interferon regulatory factor 8 for retinal tissue homeostasis and development of choroidal neovascularisation.

BACKGROUND: Microglia cells represent the resident innate immune cells of the retina and are important for retinal development and tissue homeostasis. However, dysfunctional microglia can have a negative impact on the structural and functional integrity of the retina under native and pathological conditions. METHODS: In this study, we examined interferon-regulatory factor 8 (Irf8)-deficient mice to determine the transcriptional profile, morphology, and temporospatial distribution of microglia lacking Irf8 and to explore the effects on retinal development, tissue homeostasis, and formation of choroidal neovascularisation (CNV). RESULTS: Our study shows that Irf8-deficient MG exhibit a considerable loss of microglial signature genes accompanied by a severely altered MG morphology. An in-depth characterisation by fundus photography, fluorescein angiography, optical coherence tomography and electroretinography revealed no major retinal abnormalities during steady state. However, in the laser-induced CNV model, Irf8-deficient microglia showed an increased activity of biological processes critical for inflammation and cell adhesion and a reduced MG cell density near the lesions, which was associated with significantly increased CNV lesion size. CONCLUSIONS: Our results suggest that loss of Irf8 in microglia has negligible effects on retinal homeostasis in the steady state. However, under pathological conditions, Irf8 is crucial for the transformation of resident microglia into a reactive phenotype and thus for the suppression of retinal inflammation and CNV formation.

Visual Outcome after Intravitreal Anti-VEGF Therapy for Macular Neovascularisation Secondary to Sorsby's Fundus Dystrophy: A Systematic Review.

The aim of this paper is to summarise our own and to review published experience regarding the long-term outcome of intravitreal treatment for macular neovascularisation (MNV) secondary to Sorsby's fundus dystrophy (SFD). A systematic literature search using the MeSH terms [Sorsby] and [anti-vascular endothelial growth factor (VEGF)] was conducted in NCBI/PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ScienceDirect, Google Scholar and ClinicalTrials.gov to identify publications reporting anti-VEGF treatment outcomes in SFD. Treatment outcomes were extracted for this meta-analysis from 14 publications and an own patient reporting a total of 31 cases with a mean follow-up (FU) of 54 months. Both eyes were affected in ten (32.3%) instances. Heterogenous reporting limited the comparability of the outcomes. All papers in common, however, reported satisfied to excellent responses to anti-VEGF therapy if patients were diagnosed and treated immediately after onset of symptoms. Of 20 eyes, for which visual acuity was reported before and after treatment, five worsened and seven improved by more than 1 line, whereas eight eyes maintained their function by end of the follow up, and 11 eyes (55%) maintained a driving vision (Snellen VA ≥ 0.5). Of six eyes with a VA < 0.5, VA improved in one to VA ≥ 0.5, whereas of 14 eyes with an initial VA ≥ 0.5, this dropped to <0.5 despite therapy. In MNV secondary to SFD, the delay between first symptoms and access to anti-VEGF treatment determines subretinal scar formation and thereby, functional prognosis. If treated early, this is generally favourable under regular controls and a consequent anti-VEGF treatment of MNV activity.

Results of Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Inflammatory Choroidal Neovascularization.

PURPOSE: To report the visual outcomes of intravitreal (IVT) anti-vascular endothelial growth factor (anti-VEGF) in inflammatory choroidal neovascularization (iCNV). METHODS: A retrospective study of 43 eyes of 38 patients with active choroidal neovascularization (CNV) related to ocular inflammatory disease, treated with IVT injections of anti-VEGF (bevacizumab, ranibizumab, or aflibercept), with or without associated systemic anti-inflammatory therapy, at Fattouma Bourguiba University Hospital, Monastir, Tunisia (24 eyes of 23 patients) and at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy (19 eyes of 15 patients) from January 1, 2013, to December 31, 2018. RESULTS: The mean age was 35.5 ± 16.4 years. The sex ratio male:female was 0.27. Seventeen eyes (39.5%) of 17 patients (44.7%) had only anti-VEGF injections, and 26 eyes (60.5%) of 21 patients (45.3%) had anti-VEGF injections and associated systemic anti-inflammatory therapy. Bevacizumab was injected in 36 eyes (83.7%), ranibizumab in six eyes (14%), and aflibercept in one eye (2.3%). Mean follow-up was 20.3 ± 19.2 months (range, 6-106 months). Mean visual acuity improved from 0.8 ± 0.37 logMAR (approximate Snellen equivalent 20/125) to 0.51 ± 0.42 logMAR (approximate Snellen equivalent 20/63) (P < 0.001). Mean central macular thickness on optical coherence tomography decreased from 403.7 ± 121.9 to 293.7 ± 82.8 µm (P < 0.001). Mean gain of vision was 2.9 ± 3.1 lines. The mean number of injections was 2.5. Twenty eyes (46.5%) received a single injection. There were no side effects related to the IVT injections of anti-VEGF. CONCLUSIONS: CNV is a sight-threatening complication of uveitis. IVT anti-VEGF seems to be an effective and safe treatment for iCNV when inflammation is controlled.

Macular associations of tilted disc syndrome.

Purpose: The aim of this study was to describe macular changes associated with tilted disc syndrome (TDS) using multimodality imaging. Methods: This is a retrospective observational study of the consecutive TDS cases which were studied for macular changes using color fundus photographs and optical coherence tomography (OCT). Fundus autofluorescence, fundus fluorescein angiography, and OCT angiography were performed wherever required. Results: Twenty consecutive TDS cases (36 eyes) were included. OCT showed inferior depression of all layers in specific scans and macular pathologies seen included lamellar macular hole, full-thickness macular hole, retinal pigment epithelial detachment, acute and resolved subretinal fluid, central serous chorioretinopathy, and choroidal neovascular membrane. Macular involvement was seen in 13 eyes (36.11%) while in the remaining 23 eyes, outer retinal changes were seen on OCT in 9 eyes and normal retinal layers in 14 eyes (38.89%). Conclusion: Various macular pathologies associated with TDS are described using multimodality imaging. These provide understanding of changes which can occur with TDS. It also highlights the need for recognition, differentiation from similar confusing entities, and the necessity to follow-up of these cases carefully to detect the macular changes earlier.

A novel phenotype in a family with autosomal dominant retinal dystrophy due to c.1430A > G in retinoid isomerohydrolase (RPE65) and c.37C > T in bestrophin 1 (BEST1).

PURPOSE: The c.1430A > G (Asp477Gly) variant in RPE65 has been reported in Irish and Scottish families with either an autosomal dominant retinal dystrophy (adRD) that resembles choroideremia, a vitelliform macular dystrophy or an isolated macular atrophy. We report novel features on multimodal imaging and the natural history of a family harbouring this variant in combination with the BEST1 c.37C > T (Arg13Cys) variant. METHODS: Members of a family with an adRD were examined clinically to ascertain phenotype and underwent genetic testing. Multimodal imaging included widefield colour fundus photography, quantitative autofluorescence (qAF) and spectral domain optical coherence tomography. Electrophysiology and microperimetry were also performed. RESULTS: Vision loss was attributed to foveal atrophy in the proband and choroidal neovascularisation and a vitello-eruptive lesion in one affected son. Peripheral retinal white dots corresponding to subretinal deposits were seen in three patients. The median qAF8 values in the proband (I:1) were low (40 and 101 in OD and OS) at age 79. Similarly, the qAF8 values for the middle son (II:2) were also low (100 and 87 in ODS and OS) at age 60. Electrophysiology showed disproportionate reduction in Arden ratio prior to the gradual loss of full-field responses. Microperimetry demonstrated an enlarging scotoma in the proband. CONCLUSIONS: The coexistence of the pathogenic BEST1 c.37C > T variant may modify clinical features observed in RPE65 adRD. This study expands our understanding of RPE65 adRD as a retinoid cycle disorder supported by the reduced qAF, fine white retinal dots and corresponding subretinal deposits on OCT in affected members.

RETROSPECTIVE ANALYSIS OF THE PRESENCE OF CHOROIDAL NEOVASCULARISATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE TREATMENT OF CHRONIC CENTRAL SEROUS CHORIORETINOPATHY WITH THE AID OF PHOTODYNAMIC THERAPY.

PURPOSE: Analysis of the presence of choroidal neovascularization (CNV) by optical coherence tomography angiography (OCTA) in eyes treated with photodynamic therapy in a reduced dosing regimen (HD-PDT, half dose of verteporfin) for the chronic form of central serous chorioretinopathy (cCSC). MATERIALS AND METHODS: Retrospective evaluation of OCTA findings in 54 eyes of 52 patients treated for cCSC with HD-PDT. OCTA was performed on Angioplex Zeiss Cirrus 5000 (Carl Zeiss Meditec, Dublin, CA, USA) 1 year after HD-PDT to verify changes typical of cCSC. By analyzing the results of this examination, we evaluated in particular the presence or absence of concomitant CNV and the correlation of the present CNV with the average resulting best corrected visual acuity (BCVA). RESULTS: We analyzed the OCTA findings of 54 eyes (52 patients), in which we demonstrated the presence of concomitant CNV in 35 eyes (35.2 %). Revealed CNV occurred in 82 % below the undulating hyperreflective RPE line. In eyes with CNV, the mean BCVA (72 letters ETDRS) was statistically significantly lower than in eyes without CNV (82.7 letters ETDRS) (p = 0.0179). CONCLUSION: In our retrospective evaluation of a group of patients who underwent HD-PDT for cCSC, we demonstrated with OCTA the presence of CNV in 35.2 % eyes 1 year after the treatment. We believe that the presence of type I CNV is a complication of the chronic disease itself rather than an adverse effect of HD-PDT.

Optical coherence tomography angiography findings in fellow eyes of choroidal neovascularisation associated with central serous chorioretinopathy.

AIM: To evaluate the optical coherence tomography angiography (OCTA) features of fellow eyes of patients with unilateral choroidal neovascularisation (CNV) associated with chronic central serous chorioretinopathy (CSCR). METHODS: Medical records of patients with chronic CSCR who had undergone OCT angiography of both the eyes were reviewed. Patients with evidence of unilateral CNV detected by conventional imaging (OCT, fluorescein angiography and/or indocyanine green angiography) were included in the study. The OCT and OCTA characteristics of fellow eyes were analysed. RESULTS: Forty patients (80 eyes-40 fellow eyes) with chronic CSCR with evidence of CNV in one eye were included. Mean age of the patients was 54.9±9.9 years and 82.5 % were males. Twenty-five (62.5%) fellow eyes had flat irregular pigment epithelial detachment on OCT, out of which 21 had internal hyper-reflectivity. A definite vascular network was picked up by OCTA in 9 of these 40 fellow eyes (22.5%) which was not detected on conventional imaging. In addition, two eyes had an ill-defined hyper-reflectivity, which could not be classified as a definite network at that point of time. The networks detected on OCTA in fellow eyes were mostly inactive, suggesting a subclinical neovascularisation. CONCLUSION: One-fourth of fellow eyes showed vascular network which could not be diagnosed on conventional imaging which highlights the importance of imaging both the eyes of chronic CSCR for early detection of CNV using OCTA. Further longitudinal studies are needed to assess the clinical course of such subclinical vascular networks in CSCR.