Retinal and choroidal vasoreactivity in central serous chorioretinopathy.

PURPOSE: This study aims to investigate retinal and choroidal vascular reactivity to carbogen in central serous chorioretinopathy (CSC) patients. METHODS: An experimental pilot study including 68 eyes from 20 CSC patients and 14 age and sex-matched controls was performed. The participants inhaled carbogen (5% CO2 + 95% O2) for 2 min through a high-concentration disposable mask. A 30° disc-centered fundus imaging using infra-red (IR) and macular spectral domain optical coherence tomography (SD-OCT) using the enhanced depth imaging (EDI) technique was performed, both at baseline and after a 2-min gas exposure. A parametric model fitting-based approach for automatic retinal blood vessel caliber estimation was used to assess the mean variation in both arterial and venous vasculature. Choroidal thickness was measured in two different ways: the subfoveal choroidal thickness (SFCT) was calculated using a manual caliper and the mean central choroidal thickness (MCCT) was assessed using an automatic software. RESULTS: No significant differences were detected in baseline hemodynamic parameters between both groups. A significant positive correlation was found between the participants' age and arterial diameter variation (p < 0.001, r = 0.447), meaning that younger participants presented a more vasoconstrictive response (negative variation) than older ones. No significant differences were detected in the vasoreactive response between CSC and controls for both arterial and venous vessels (p = 0.63 and p = 0.85, respectively). Although the vascular reactivity was not related to the activity of CSC, it was related to the time of disease, for both the arterial (p = 0.02, r = 0.381) and venous (p = 0.001, r = 0.530) beds. SFCT and MCCT were highly correlated (r = 0.830, p < 0.001). Both SFCT and MCCT significantly increased in CSC patients (p < 0.001 and p < 0.001) but not in controls (p = 0.059 and 0.247). A significant negative correlation between CSC patients' age and MCCT variation (r = - 0.340, p = 0.049) was detected. In CSC patients, the choroidal thickness variation was not related to the activity state, time of disease, or previous photodynamic treatment. CONCLUSION: Vasoreactivity to carbogen was similar in the retinal vessels but significantly higher in the choroidal vessels of CSC patients when compared to controls, strengthening the hypothesis of a choroidal regulation dysfunction in this pathology.

Central serous chorioretinopathy and angioid streaks: coincidental?

BACKGROUND: To report an unusual case of central serous chorioretinopathy in a patient with angioid streaks. CASE PRESENTATION: The authors describe a case report of a 26-year old male patient presenting acute scotoma and metamorphopsia in OD. He had been diagnosed with angioid streaks complicated with choroidal neovascularization and referred to us for treatment. The patient presented an ETDRS score of 85 letters (20/20) in OD and in OS. The anterior segment examination was unremarkable. Fundoscopy revealed bilateral angioid streaks (AS) and peau d'orange, as well as a small neurosensory retinal detachment in the macula of OD. A multimodal retinal analysis, including fundus photography, infra-red and fundus autofluorescence imaging, spectral-domain optical coherence tomography, optical coherence tomography angiography, fluorescein and indocyanine green angiography was performed. The diagnosis of central serous chorioretinopathy was made in the absence of any identifiable choroidal neovascularization. He was submitted to half-dose photodynamic therapy with verteporfin. One month later, he reported no visual complaints, his vision was 85 letters (20/20) in OD and a complete resolution of the sub-retinal fluid was registered. No signs of choroidal neovascularization were detected on the optical coherence tomography angiography (OCTA). A complete medical workup evaluation was made to exclude systemic diseases usually associated with AS. CONCLUSIONS: To the authors' knowledge, this is the second reported case of CSC associated with angioid streaks. The focal abnormalities in the Bruch's membrane and the irregular vascular choriocapillary network associated with AS might predispose to CSC.

Cerebral Neurovascular Coupling Impairment in Central Serous Chorioretinopathy.

BACKGROUND: Central serous chorioretinopathy (CSCR) is a chorioretinal disorder resulting from choroidal hyperpermeability. Its comorbidities as hypertension, coronary disease, and psychological stress, suggest that it might reflect a more generalized vascular dysfunction. OBJECTIVES: The aim of the study was to assess the cerebrovascular regulation integrity, using cerebral autoregulation (CA), carbon dioxide vasoreactivity (VR), and neurovascular coupling (NVC) in CSCR. METHODS: This observational pilot study included 20 CSCR patients and 14 age- and sex-matched controls. A State-Trait Anxiety Inventory (STAI) inquiry was full-filled. Continuous measurement of cerebral blood flow velocity (CBFV), arterial blood pressure, heart rate, and end-tidal carbon dioxide was performed. VR was assessed during hypercapnia (inhaling carbogen gas) and hypnocapnia (hyperventilation). For NVC, the CBFV relative increase during mental activation using the N-Back Task was calculated. RESULTS: No significant differences in systemic hemodynamic parameters, CA or VR, were found between both groups. During the NVC performance, the average CBFV rise during mental stress was significantly lower in CSCR (p = 0.011). A significant negative correlation was found between STAI scores and NVC. CONCLUSIONS: CSCR patients presented a significantly impaired cerebral NVC compared to controls, supporting the theory of a potential systemic vascular dysfunction. Stress could be related to this NVC impairment.

Correlation Between Ophthalmologic and Neuroradiologic Findings in Type 1 Neurofibromatosis.

BACKGROUND: Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings. METHODS: This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established. RESULTS: Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings. CONCLUSIONS: This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients.

Longitudinal Retinal Changes Induced by Hydroxychloroquine in Eyes without Retinal Toxicity.

INTRODUCTION: This study aimed to evaluate the longitudinal changes in retinal layer thickness in patients treated with hydroxychloroquine without retinal toxicity. METHODS: This is a longitudinal retrospective study of patients taking hydroxychloroquine followed in a hydroxychloroquine retinal toxicity screening program of a tertiary hospital between January 2010 and April 2019. Patients who performed 2 optical coherence tomography (OCT) scans at least 1 year apart were included. All subjects with hydroxychloroquine suspected or confirmed retinal toxicity, glaucoma, retinal pathology, or poor segmented images were excluded. Spectral-domain optical coherence tomography (Spectralis HRA-OCT, Heidelberg) was used to evaluate the macular area. Automatically segmented ETDRS retinal thickness maps were compared between the first and the last OCT evaluation available. Full retina (FR), inner retina (IRL), ganglion cells (GCL), inner nuclear (INL), and outer retina (ORL) layer thicknesses were measured in the foveolar, paracentral, and peripheral area. RESULTS: The population included 144 eyes of 144 patients. The mean interval between OCT scans was 38.1 ± 18.4 months, and the mean cumulative dose was 406.9 ± 223.9 g. Foveolar (p = 0.040, p = 0.006, and p = 0.001, respectively) and paracentral (p = 0.006, p = 0.001, and p = 0.005, respectively) FR, IRL, and GCL decreased overtime. No differences were found in INL or ORL. A very weak correlation was found between age and foveal IRL change overtime (p = 0.037; R = 0.175), as well as between the hydroxychloroquine time of use and foveal GCL variation (p = 0.032; R = 0.179). CONCLUSION: Hydroxychloroquine was found to cause progressive thinning of the inner retinal layers, specifically in the GCL of the foveolar and paracentral areas, but no changes were observed in the outer retina.

Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success.

PURPOSE: To evaluate functional and anatomical outcomes after aflibercept in patients with diabetic macular edema (DME) with poor response to bevacizumab. METHODS: We retrospectively reviewed patients with DME recalcitrant to bevacizumab who were switched to aflibercept between January and December 2015. All patients had a minimal follow-up of three months before the conversion and underwent at least three injections of bevacizumab. Functional outcome consisted in best corrected visual acuity (VA). Anatomical outcomes were demonstrated through central macular thickness (CMT) measured by optical coherence tomography. RESULTS: Forty-nine eyes of 34 subjects were reviewed. Mean VA improved from 0.55 ± 0.32 logMAR to 0.46 ± 0.33 logMAR (p = 0.038). Mean CMT decreased from 473 ± 146 µm to 349 ± 85 µm (p < 0.001). Twelve eyes (24%) demonstrated absence of macular edema after aflibercept. Previous bevacizumab exposure did not correlate with different outcomes. The variation of VA in response to aflibercept was significantly superior in the group with poorer VA before the switch (mean variation of -0.097 ± 0.21 logMAR) when compared to eyes with VA < 0.4 logMAR (mean variation of +0.019 ± 0.090 logMAR; p = 0.036). The same scenario was verified for anatomical outcomes as eyes with poor vision before the switch (≥0.4 logMAR) achieved superior reduction in CMT in response to aflibercept (mean CMT variation of -157 ± 171 µm versus -49.5 ± 39.9 µm; p < 0.01). Pre-switch CMT was a predictor of CMT reduction after switching (B = -0.945; confidence interval 95% -1.1; -0.76; p < 0.001). CONCLUSIONS: Conversion to aflibercept for persistent DME resulted in functional and anatomical improvements and these outcomes were not influenced by previous bevacizumab exposure. Pre-switch CMT was a predictor of anatomical changes after aflibercept.

Spectral-Domain Optical Coherence Tomography as a Potential Biomarker in Huntington's Disease.

BACKGROUND: Spectral-domain optical coherence tomography has been used in several neurological conditions, and peripapillary and macular measurements have been proposed as potential biomarkers in these disorders. The aim of this study was to investigate retinal and choroidal changes in Huntington's disease and to evaluate any potential correlation with the stage of the disease. METHODS: A cross-sectional observational study compared patients with Huntington's disease and controls. Patients were evaluated using the Unified Huntington's Disease Rating Scale. Spectral-domain optical coherence tomography with enhanced depth imaging was used, and peripapillary choroidal and retinal nerve fiber layer thickness and macular retinal and choroidal thickness were evaluated. RESULTS: Fifteen eyes of 8 patients and 16 eyes of 8 sex-, age-, and mean refractive error-matched healthy controls were included. Average (231.3 ± 52.8 vs 296.2 ± 57.1, P = 0.033), central (341.8 ± 70.5 vs 252.0 ± 57.9, P = 0.015), and inferior (225.3 ± 57.9 vs 313.8 ± 55.2, P = 0.007) macular choroidal thickness were significantly reduced in patients, in comparison with controls. No differences were observed in macular retina or peripapillary retinal and choroidal measurements. However, there was a negative correlation between Total Motor Score of the Unified Huntington's Disease Rating Scale and average (r(2) = 0.585, P = 0.027), superior (r(2) = 0.653, P = 0.015), nasal (r(2) = 0.642, P = 0.017), and inferior (r(2) = 0.574, P = 0.029) macular retinal thickness. CONCLUSIONS: Our results suggest that both the choroidal and retinal macula are altered in Huntington's disease and may become useful biomarkers for monitoring neurodegeneration in this disease. The involvement of the choroid may also support the recent findings of vascular involvement in Huntington's disease.

Alström syndrome mimicking spasmus nutans: report of a novel ALMS1 variant.

We report the case of an otherwise healthy 6-year-old girl presenting with poor visual acuity, photophobia, and abnormal eye and head movements who was initially diagnosed with spasmus nutans. A remote history of presumed viral cardiomyopathy and further electroretinography testing raised suspicion for Alström syndrome. She was diagnosed with a novel ALMS1 variant.

ILUVIEN® in diabetic macular edema that persists or recurs despite treatment: Results from the Retina.pt® RIVER audit.

PURPOSE: Persistent diabetic macular edema (DME) remains a problem in clinical practice, with many patients having a suboptimal response to the standard of care (SOC). Evidence supports the long-term efficacy of intravitreal fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients that have responded sub-optimally, although there is still scarce data from real-world Portuguese practices. We aimed to monitor the current SOC in selected Portuguese practices prior to FAc implantation and then assess the long-term effectiveness and safety of the FAc implant. SETTINGS: The study included patient data from five Portuguese public hospitals. DESIGN: This was a non-interventional, multicenter audit of data collected from Retina.pt registry from patients with persistent or recurrent DME despite treatment. METHODS: Outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Results were compared at regular times over 36 months. RESULTS: This study included 222 eyes from 152 patients. A significant decrease in BCVA (P < 0.001) and a significant increase in CMT (P = 0.013) were observed prior to FAc. A significant increase in BCVA was registered at 6 months after FAc implant administration (P < 0.001), which was maintained during follow-up. No relevant changes in IOP were observed. Treatment burden was reduced as a result of treatment with FAc (P < 0.001 for anti-VEGF, corticosteroids, or both treatments) in the full population. CONCLUSIONS: In Portuguese practice, data showed that pre-FAc implantation, some patients did not respond to SOC treatment and/or they were undertreated. Following FAc implant administration, there were rapid, sustained, long-term visual and anatomical improvements, and a marked reduction in treatment burden.

Peripapillary and Subfoveal Choroidal Thickness in Retinal Vein Occlusions.

Purpose: This work aimed to longitudinally assess the peripapillary (PPCT) and subfoveal (SFCT) choroidal thickness (CT), in patients diagnosed with central (CRVO) or branch retinal vein occlusions (BRVO), correlating SFCT with central macular thickness (CMT) and PPCT with peripapillary retinal nerve fiber layer thickness (pRNFL). Patients and Methods: This was a retrospective longitudinal study of 71 eyes from 71 patients with treatment-naïve retinal vein occlusion (24 CRVO and 40 BRVO). Spectral-domain optical coherence tomography (SD-OCT, Spectralis HRA-OCT, Heidelberg) was used to measure PPCT, SFCT, pRNFL and CMT of the affected and fellow eyes at baseline (acute phase) and at 3 and 9 months post anti-VEGF treatment. IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. A p-value ≤0.05 was considered statistically significant. Results: Affected eyes presented a thicker baseline PPCT and SFCT compared to their fellow eyes both in CRVO and BRVO (p < 0.05). Both groups presented a significant decrease of PPCT in the affected eyes at 3 months compared to baseline (p < 0.05). At 9 months, compared to 3 months, PPCT remained stable (p > 0.05). Similarly, affected eyes' SFCT significantly decreased at 3 months (p < 0.05) in both groups. At 9 months, compared to 3 months, SFCT decreased in the CRVO patients (p = 0.047) but remained stable in the BRVO patients (p = 0.850). No correIations between SFCT and CMT were seen at any timepoint in both groups (p > 0.05). PPCT correlates with pRNFL in CRVO at 3 months, although no other correlations were found during the follow-up. In BRVO, PPCT did not show any significant correlation with pRNFL. Conclusion: Both in CRVO and BRVO eyes, PPCT and SFCT at diagnosis are significantly thicker compared to the fellow eye, suggesting a possible increase in CT immediately after the occlusion, which is followed by a decrease at an early follow-up stage.

Longitudinal multimodal functional macular analysis after half-dose photodynamic therapy for central serous chorioretinopathy.

BACKGROUND: Half-dose photodynamic therapy (HD-PDT) has been widely used for central serous chorioretinopathy (CSC) with good anatomical results. However, long-term functional outcomes after this treatment remain uncertain. This study aimed a longitudinal multimodal macular assessment, correlating functional and anatomical outcomes. METHODS: This is a retrospective study performed in a tertiary referral center including 111 eyes from 95 CSC patients. Data on best corrected visual acuity (BCVA), central macular thickness (CMT), central retinal sensitivity (CRS) using microperimetry (MP) and multifocal electroretinography (mfERG) at baseline and 3, 6, 12, 18, 24, 36, 48 and 60 months after treatment were registered. A correlation analysis was performed. RESULTS: Mean follow-up was 34.5 ± 26.3 months. A significant improvement in BCVA and CMT was registered in all the visits. CRS significantly improved until 24 months (p < 0.001 at 12 months, p < 0.05 at 24 months), worsening afterwards. The mfERG amplitude of N1 and P1 waves significantly improved in the first 12 months, aggravating afterwards. The implicit time improved until 24 months, deteriorating after 48 months. This long-term decline was also described in some inactive untreated fellow eyes CONCLUSIONS: A multimodal longitudinal analysis of CSC patients after HD-PDT shows that, after the first 12 to 24 months, the significant sustained improvement in BCVA and CMT is not paired by a sustained improvement in macular sensitivity or electrical response. This long-term functional deterioration might result from the disease itself and not directly from the treatment .

A novel mutation (Cys83Tyr) in the second zinc finger of NR2E3 in enhanced S-cone syndrome.

BACKGROUND: Enhanced S-cone syndrome (ESCS) is an autosomal recessive retinal disorder characterized by an increased number of S-cones over L/M cones and rods. Mutations in the NR2E3 gene, encoding a photoreceptor-specific nuclear receptor, are identified in patients with ESCS. The purpose of this study is to report the ophthalmic features of a 25-year-old Portuguese male with a typical ESCS phenotype and a novel homozygous NR2E3 mutation. METHODS: The patient underwent a detailed ophthalmic examination including fundus photography, fluorescein angiography (FAF), fundus autofluorescence imaging (FAI), and spectral domain optical coherence tomography (SD-OCT). Full-field electroretinography (ERG), S-cone ERG, and multifocal ERG were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction amplification and direct sequencing. RESULTS: The patient had poor visual acuity but good color vision. Funduscopy showed degenerative changes from the vascular arcades to the midperipheral retina. The SD-OCT revealed macular schisis and cystoid changes that had no fluorescein leakage. The posterior pole showed diffusely increased autofluorescence compared with eccentric areas in both eyes. International-standard full-field ERG showed the typical pathognomonic changes associated with ESCS and the short-wavelength flash ERG was simplified, delayed, and similar to the standard photopic flash ERG. Multifocal ERG showed widespread delay and reduction. Genetic analysis revealed a novel homozygous mutation (p.C83Y), which resides in the second zinc finger of the DNA-binding domain. CONCLUSIONS: This homozygous mutation is likely to affect binding to target DNA sites, resulting in a non-functional behavior of NR2E3 protein. It is associated with a typical form of ESCS with a nondetectable rod response and reduced/delayed mfERG responses at all eccentricities.

Long term outer retinal changes in central serous chorioretinopathy submitted to half-dose photodynamic therapy.

PURPOSE: To evaluate long-term changes in the foveal and parafoveal outer retina after half-dose photodynamic therapy (HD-PDT) in central serous chorioretinopathy (CSC). METHODS: Retrospective study including CSC patients submitted to HD-PDT. Best corrected visual acuity (BCVA) was evaluated. Spectral-domain optical coherence tomography automatic segmentation algorithm was used and data on retinal, inner retinal, outer retinal and outer nuclear layers (ONL) in both foveal 1 mm (C) and parafoveal 3 mm ETDRS circles for the superior, nasal, inferior and temporal sectors, were obtained at baseline and 3, 12 and 24 months post-treatment. Subfoveal choroidal thickness, photoreceptors' outer segment thickness, subretinal fluid (SRF) height and width were also measured. RESULTS: Twenty-one eyes of 15 patients were included. At baseline, the mean ONL thickness in the foveal area was significantly thinner in affected eyes compared to their fellow unaffected ones (55,50 ± 32,75 µm vs 93,00 ± 17,0 µm; p = 0,011), and was negatively correlated to logMAR BCVA (R=-0,601, p = 0,008) ONL thickness increased by 10,94 ± 11,88 µm at 24 months in the foveal area, and all the parafoveal sectors presented a similar increase. Baseline SRF width was significantly correlated with baseline BCVA (R1 = 0,483, p = 0,036), and with ONL thickness in all sectors. CONCLUSION: In our study we found a significant long-term increase in foveal and parafoveal ONL thickness in CSC after HD-PDT, suggesting that this seems to be a safe treatment for the outer retina. This is the first study mapping the outer retinal changes in the macular area to 24 months follow up.

Covid-19 Impact on Macular Neovascularization and Retinal Vein Occlusion Treatment: Single-Center Experience.

PURPOSE: The aim of this study was to evaluate whether the coronavirus disease 19 (COVID-19) pandemic resulted in undertreatment and subsequent loss of visual acuity (VA) in patients with macular neovascularization (MNV) or retinal vein occlusion (RVO) regularly treated with intravitreal antivascular endothelial growth factor injections. METHODS: Single-center, retrospective study of patients scheduled for treatment between March 19 and June 1, 2020, the national mandatory quarantine period. Patients' demographics, VA, and scheduled treatment during this period were reviewed via medical records. All patients were analyzed regarding treatment attendance rates. The visual impact of COVID-19 was assessed in patients who had been treated and presented a stable VA for >6 months before the beginning of the quarantine. RESULTS: This study included 927 eyes from 769 patients. The attendance rate increased throughout the study timeframe (p < 0.001) and correlated negatively with higher patient's age (r = -0.142; p = 0.005). Patients with age-related macular degeneration (67.6%) had lower attendance rates (p = 0.007) and were older (p < 0.001). The visual impact analysis included 400 eyes from 325 patients. The average VA variation throughout this period was -1.7 ± 8.4 ETDRS letters and was similar in different retinal pathologies (p = 0.334). VA variation did not correlate with the number of missed treatments per patient (r = 0.100; p = 0.150). The prevalence of subretinal fluid and intraretinal fluid, as well as central retinal thickness decreased significantly throughout the study period (p values of <0.001, <0.001, and 0.032, respectively). CONCLUSION: The COVID-19 pandemic had a significant impact on the attendance rate of patients with MNV or RVO to their scheduled treatments, which was higher in the first week of mandatory quarantine. Nevertheless, VA did not decrease significantly during this period, with a limited VA variation regardless of primary retinal disorder and morphological parameters even improved in the eyes included in the visual impact analysis.

Idiopathic Acute Exudative Polymorphous Vitelliform Maculopathy: Insight into Imaging Features and Outcomes.

The authors describe imagiological findings in idiopathic exudative polymorphous vitelliform maculopathy. A 41-year-old woman complained of bilateral blurry vision. Best-corrected visual acuity was 20/20 bilaterally. Bilateral small serous neurosensory detachments in the fovea were seen at fundoscopy and confirmed by spectral-domain optical coherence tomography. Fluorescein angiography was unremarkable. Indocyanine green angiography presented discrete hyperfluorescent spots on the posterior pole. Later, more bleb-like lesions with a vitelliform appearance and hyperautofluorescent on blue fundus autofluorescence were detected. One year later, a complete resolution of the fluid was observed. To conclude, multimodal evaluation of patients with idiopathic exudative polymorphous vitelliform maculopathy is essential for the correct diagnosis of this disease.

DR|GRADUATE: Uncertainty-aware deep learning-based diabetic retinopathy grading in eye fundus images.

Diabetic retinopathy (DR) grading is crucial in determining the adequate treatment and follow up of patient, but the screening process can be tiresome and prone to errors. Deep learning approaches have shown promising performance as computer-aided diagnosis (CAD) systems, but their black-box behaviour hinders clinical application. We propose DR|GRADUATE, a novel deep learning-based DR grading CAD system that supports its decision by providing a medically interpretable explanation and an estimation of how uncertain that prediction is, allowing the ophthalmologist to measure how much that decision should be trusted. We designed DR|GRADUATE taking into account the ordinal nature of the DR grading problem. A novel Gaussian-sampling approach built upon a Multiple Instance Learning framework allow DR|GRADUATE to infer an image grade associated with an explanation map and a prediction uncertainty while being trained only with image-wise labels. DR|GRADUATE was trained on the Kaggle DR detection training set and evaluated across multiple datasets. In DR grading, a quadratic-weighted Cohen's kappa (κ) between 0.71 and 0.84 was achieved in five different datasets. We show that high κ values occur for images with low prediction uncertainty, thus indicating that this uncertainty is a valid measure of the predictions' quality. Further, bad quality images are generally associated with higher uncertainties, showing that images not suitable for diagnosis indeed lead to less trustworthy predictions. Additionally, tests on unfamiliar medical image data types suggest that DR|GRADUATE allows outlier detection. The attention maps generally highlight regions of interest for diagnosis. These results show the great potential of DR|GRADUATE as a second-opinion system in DR severity grading.

Combined treatment with intravitreal bevacizumab and laser photocoagulation for exudative maculopathy in facioscapulohumeral muscular dystrophy.

PURPOSE: To report a rare case of exudative maculopathy in a patient with facioscapulohumeral muscular dystrophy (FSHD), and its management. METHODS: Observational case report. RESULTS: A 62-year-old man with genetically confirmed FSHD was referred to our department complaining of decreased visual acuity in his left eye. At presentation, right eye examination was unremarkable and best-corrected visual acuity (BCVA) was 20/20. Left eye BCVA was 20/100 and it presented a dense cataract with the evidence of macular lipid exudation. Cataract surgery combined with intravitreal bevacizumab improved BCVA to 20/20. Postoperative fundus examination disclosed focal macular retinal microvascular dilations with lipid exudation inferotemporal to the fovea. Fluorescein angiography highlighted these macular telangiectatic abnormalities but no peripheral lesions were detected. Spectral domain optical coherence tomography (SD-OCT) showed mild temporal retinal thickening, sparing the fovea. A diagnosis of exudative maculopathy due to macular telangiectasia secondary to FSHD was established. One year later, his left eye vision dropped to 20/32 and macular SD-OCT showed an aggravation of the intraretinal fluid and exudation. He was then submitted to a second intravitreal injection of bevacizumab followed by one angio-guided focal laser photocoagulation session, with a significant improvement. Twelve months later, his BCVA remained 20/20 on both eyes with no recurrence of exudation. CONCLUSION: The present work shows that in cases of visual-threatening macular exudation, intravitreal anti-vascular endothelial growth factor injections combined with focal laser photocoagulation may be a safe and effective treatment. This article also highlights that all FSHD patients should be screened for asymptomatic retinal vascular disorders.