CHOROIDAL INVOLVEMENT IN HEREDITARY TRANSTHYRETIN AMYLOIDOSIS PATIENTS.

PURPOSE: To compare the choroidal characteristics between the eyes of patients with and without hereditary transthyretin amyloidosis. METHODS: Case-control observational study with choroidal thickness and vasculature evaluation by optical coherence tomography with enhanced depth imaging protocol of the macula. RESULTS: The study included 332 eyes: 166 eyes of hereditary transthyretin amyloidosis patients and 166 eyes of healthy patients. Mean age was similar between groups (P = 0.979). For hereditary transthyretin amyloidosis patients, on average, in all sectors analyzed (in the full 5 mm-width image [G] and also in 1-mm-width central [C], nasal [N], and temporal [T] sectors), there was a higher stromal area, a lower choroidal thickness, and a lower choroidal vascularity index, compared with the control group. The linear mixed models revealed no differences according to the systemic treatment groups. CONCLUSION: Hereditary transthyretin amyloidosis patients showed statistically significant differences in choroidal characteristics, compared with eyes without pathology. These age-related and statistically significant changes compared with the healthy eyes may help in the future to better monitor the systemic hereditary transthyretin amyloidosis disease and complement other systemic evaluations, including on clinical trials to analyze more objectively, the results of new therapies.

Changes in Ganglion Cell Layer Thickness after Treatment with the 0.2 µg/day Fluocinolone Acetonide Implant in Vitrectomized and Nonvitrectomized Eyes with Diabetic Macular Edema.

INTRODUCTION: The objective of this study is to compare changes in ganglion cell layer (GCL) between vitrectomized and nonvitrectomized eyes with diabetic macular edema (DME) over a 2-year period following treatment with 0.2 µg/day fluocinolone acetonide (FAc) implant. METHODS: Eighteen vitrectomized (group 1) and 8 nonvitrectomized (group 2) eyes were included in this cohort study. Changes in central macula GCL thickness were measured using the Spectralis spectral domain-optical coherence tomography at baseline and 6, 12, and 24 months of follow-up. Other parameters analyzed included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intraocular pressure (IOP). RESULTS: Treatment with the FAc implant led to small reductions in mean global GCL thickness versus baseline and contrasts with the control group that was stable or slightly increased versus baseline. FAc therapy also led to improvements in mean BCVA and CFT that were observed at Month 6 and maintained to Month 24. For vitrectomized and nonvitrectomized eyes, no differences were observed between mean global GCL, BCVA, and CFT values during follow-up. Linear correlations revealed that in all groups mean BCVA at Month 24 positively correlated with mean GCL thickness at baseline and at Month 24. IOP remained stable throughout the 24 months. CONCLUSION: There was no evident retinal neurodegeneration in the 2-year period following treatment with FAc in both groups. GCL thickness may be a useful biomarker for assessing safety and effectiveness in patients with DME.

A Systematic Review of Artificial Intelligence Applications Used for Inherited Retinal Disease Management.

Nowadays, Artificial Intelligence (AI) and its subfields, Machine Learning (ML) and Deep Learning (DL), are used for a variety of medical applications. It can help clinicians track the patient's illness cycle, assist with diagnosis, and offer appropriate therapy alternatives. Each approach employed may address one or more AI problems, such as segmentation, prediction, recognition, classification, and regression. However, the amount of AI-featured research on Inherited Retinal Diseases (IRDs) is currently limited. Thus, this study aims to examine artificial intelligence approaches used in managing Inherited Retinal Disorders, from diagnosis to treatment. A total of 20,906 articles were identified using the Natural Language Processing (NLP) method from the IEEE Xplore, Springer, Elsevier, MDPI, and PubMed databases, and papers submitted from 2010 to 30 October 2021 are included in this systematic review. The resultant study demonstrates the AI approaches utilized on images from different IRD patient categories and the most utilized AI architectures and models with their imaging modalities, identifying the main benefits and challenges of using such methods.

Epiretinal membrane vitrectomy: outcomes with or without cataract surgery and a novel prognostic factor for cystoid macular edema.

PURPOSE: To assess the outcomes of vitrectomy with or without cataract surgery for the treatment of idiopathic ERM in phakic eyes and evaluate predictors of functional and anatomical outcomes. METHODS: Retrospective cohort of consecutive phakic ERM eyes distributed in three groups: a) combined (phacovitrectomy) group, b) PPV-only group, and c) consecutive group (PPV followed by cataract surgery). Main outcomes were final visual acuity (VA) and cystoid macular edema (CME) occurrence. Potential predictors of VA or CME included clinical variables and SD-OCT parameters. RESULTS: A total of 108 eyes were included in this study. There were no differences in the final VA between consecutive and combined groups (0.22 vs 0.10 logMAR, p = 0.851). Twelve eyes from the combined group (23%) and one eye from the PPV-only group presented CME (p = 0.001). There were no differences between postoperative CME occurrence in combined versus consecutive group (12 vs 7, p = 0.38). The presence of cotton-ball sign predicted the development of CME [OR 2.86 (95%CI 1.01-8.18), p = 0.049] while separated ERM-ILM complex was found to be protective [OR 0.25 (95%CI 0.08-0.77), p = 0.015]. CONCLUSIONS: Functional and anatomical results of PPV with ERM and ILM peeling combined with cataract surgery was equivalent to the consecutive procedure, with both strategies being effective. Separated ERM-ILM complex has prognostic value in these patients, as its presence at baseline was found to be protective for postoperative CME.

Optical Coherence Tomography Biomarkers: Vitreous Status Influence in Outcomes for Diabetic Macular Edema Therapy with 0.19-mg Fluocinolone Acetonide Implant.

BACKGROUND: The 0.19-mg fluocinolone acetonide (FAc) implant (ILUVIEN®; Alimera Sciences Ltd., Hampshire, UK) was approved for the treatment of vision impairment associated with chronic and refractory diabetic macular edema (DME). OBJECTIVES: To quantitatively assess functional and structural features in nonvitrectomized and vitrectomized DME patients after being treated with an FAc implant. METHODS: Retrospective review of patients with DME receiving a single intravitreal injection of the FAc implant. The study was designed to analyze the presence of quantitative structural OCT biomarkers at baseline and 12 months after FAc therapy according to vitreous status. RESULTS: A total of 41 eyes from 30 patients were included in this study. At 12 months after injection, vitrectomized patients had a lower central foveal thickness (p = 0.017) and fewer hyperreflective dots (p = 0.028) compared with nonvitrectomized. Thirty (73%) patients presented a significant functional improvement with 17 (42%) increasing at least 15 ETDRS letters. Overall, 22 (54%) eyes had a complete resolution of DME at the 12-month visit. Patients who needed additional therapy had a higher prevalence of subretinal fluid (42 vs. 3%, p = 0.005) at baseline. CONCLUSIONS: This study supports the effectiveness of the FAc implant and reports significant changes at 12 months after FAc injection.

Inverted internal limiting membrane flap technique in the surgical treatment of macular holes: 8-year experience.

PURPOSE: To evaluate the ellipsoid zone (EZ) structural recovery, hole closure rate, and visual acuity improvement after inverted internal limiting membrane (ILM) flap technique. METHODS: Retrospective cohort of eyes affected by idiopathic macular holes (MH) that underwent pars plana vitrectomy combined with inverted ILM flap technique in a tertiary center, over an 8-year period (2011-2019). The main outcomes were the postoperative qualitative analysis of EZ structure on spectral-domain optical coherence tomography, hole closure rate, and best-corrected visual acuity (BCVA) improvement of ≥ 0.3 units in the logarithm of minimal angle of resolution (logMAR) scale. RESULTS: Our study included 76 eyes of 72 patients; 65% were female, with a mean age of 70 ± 8 years-old. Median (range) follow-up was 21 (3-92) months. Hole closure rate was 92%. Structural defects in EZ were observed in 66% of closed holes (EZ atrophy in 33%, EZ disruption in 22%, and EZ thinning in 11%). The mean final BCVA was 0.5 ± 0.4 logMAR (Snellen 20/63), but visual acuity improvement occurred in 80% of the eyes. Final BCVA was significantly worse in eyes with EZ atrophy compared with eyes with EZ disruption (0.75 vs. 0.36 logMAR, p = 0.004) and EZ thinning (0.75 vs. 0.32 logMAR, p = 0.015). In multivariate regression, minimum linear diameter (OR 1.01; IC 95% 1.01-1.02) independently predicted a final BCVA (logMAR) < 0.3 units. CONCLUSION: Inverted ILM flap technique provided a hole closure rate above 90%, similar to previous studies. Although the modest value of the final BCVA, a significant visual acuity improvement occurred in most eyes. Structural defects of EZ were found in more than half of closed MHs after surgery. Evidence of postoperative retinal atrophy was associated with a worse visual outcome.

Dealing with rhegmatogenous retinal detachment in patients under 40 years old: a tertiary center results.

PURPOSE: The risk of rhegmatogenous retinal detachment (RRD) increases with age, but some studies report a secondary peak in younger patients. Since visual recovery in RRD depends on surgical treatment and, considering the personal, social and economic burden of low vision in the working-age population, our purpose was to analyze the features and outcomes of RRD in young patients. METHODS: Clinical data of patients under 40 years old submitted to surgery for first time RRD, consecutively selected between 2016 and 2019, was analyzed. Patients with less than 3 months follow-up were excluded. RESULTS: Eighty-nine eyes from 89 patients were included. Mean age was 31.2 ± 7.8 years (minimum 10 years) and 56% were female gender. Most patients (63%) had high myopia. Pars plana vitrectomy (79%) alone, combined with scleral buckling (1%) or scleral buckling alone (20%) was performed. Primary anatomical success was 72%, and final anatomical success was 91%. Final visual acuity of 20/40 or better was achieved in 29% of cases, but 28% remained under 20/400. The presence of myopia (p = 0.022), localized RRD (p = 0.007) and attached macula at presentation (p < 0.001) was associated with a better final visual acuity. CONCLUSION: Management of RRD in young patients must be thorough. In younger patients, anatomical outcomes may be worse than in older patients. Myopia may be recognized as a major risk factor for RRD in this age group, but also as a protective factor for retinal function after surgery.

Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner.

BACKGROUND: Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms. METHODS: These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central. RESULTS: The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy. CONCLUSIONS: A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.

Vitrectomy Outcomes in Eyes with Tractional Diabetic Macular Edema.

PURPOSE: To evaluate pars plana vitrectomy (PPV) outcomes in cases with tractional diabetic macular edema (tDME). METHODS: We conducted a single-center retrospective study with a follow-up of 12 months. Forty-six eyes with tDME of 38 patients submitted to PPV between 2013 and 2015 were assessed. A standard PPV was performed and surgical outcomes were registered at the 3-, 6-, and 12-month follow-up. RESULTS: The baseline median best corrected visual acuity (BCVA) in ETDRS (Early Treatment Diabetic Retinopathy Study) letters and the median central foveal thickness (CFT) were 43.0 letters and 491.0 µm, respectively. At the 12-month follow-up, a median decrease in CFT of 232.7 µm was observed. A CFT < 300 µm was achieved in 65.2% of the cases (52.2% needing no further treatment); a BCVA improvement by ≥10 letters was achieved in 60.0%, but there was a decrease of ≥10 letters in 13.0% of the cases. DME recurrence was observed in 10.9% of the cases, with a median time of development after vitrectomy of 6 months. As a major postoperative complication, a macular hole was observed in 1 patient (2.1%). CONCLUSIONS: In our series, PPV for tDME induced an improvement in retinal thickening and visual outcome in more than 50% of the cases, with low recurrence rates and a low number of postoperative complications.

Information-Theoretical Criteria for Characterizing the Earliness of Time-Series Data.

Biomedical signals constitute time-series that sustain machine learning techniques to achieve classification. These signals are complex with measurements of several features over, eventually, an extended period. Characterizing whether the data can anticipate prediction is an essential task in time-series mining. The ability to obtain information in advance by having early knowledge about a specific event may be of great utility in many areas. Early classification arises as an extension of the time-series classification problem, given the need to obtain a reliable prediction as soon as possible. In this work, we propose an information-theoretic method, named Multivariate Correlations for Early Classification (MCEC), to characterize the early classification opportunity of a time-series. Experimental validation is performed on synthetic and benchmark data, confirming the ability of the MCEC algorithm to perform a trade-off between accuracy and earliness in a wide-spectrum of time-series data, such as those collected from sensors, images, spectrographs, and electrocardiograms.

Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30M familial amyloid polyneuropathy.

PURPOSE: Glaucoma is the leading cause of irreversible blindness in familial amyloidotic polyneuropathy (FAP) patients. Erythropoietin (EPO) is a cytokine that has been shown to play a role in neuroprotection and is endogenously produced in the eye. EPO levels in the aqueous humor are increased in eyes with glaucoma. In this study, we evaluated the EPO concentration in the aqueous humor of FAP and non-FAP patients, with and without glaucoma. METHODS: Undiluted aqueous humor samples were obtained from 42 eyes that underwent glaucoma surgery, phacoemulsification, or vitrectomy. EPO concentration in the aqueous humor and blood were measured using the Immulite 2000 Xpi using an automatic analyzer (Siemens Healthcare Diagnostics). RESULTS: The mean EPO concentration in the aqueous humor of non-FAP glaucoma eyes group 2 (75.73±13.25 mU/ml) was significantly higher than non-FAP cataract eyes (17.22±5.33 mU/ml; p<0.001), FAP glaucoma eyes (18.82±10.16 mU/ml; p<0.001), and FAP nonglaucoma eyes (20.62±6.22 mU/ml; p<0.001). There was no statistically significant difference between FAP nonglaucoma eyes versus non-FAP cataract eyes (p = 0.23) and FAP glaucoma eyes versus FAP nonglaucoma eyes (p = 0.29). In the glaucoma groups, there was no correlation between the aqueous humor EPO concentration and the ocular pressure (p = 0.95) and mean deviation (p = 0.41). There was no correlation between the EPO serum concentration and EPO aqueous humor concentration in our patients (p = 0.77). CONCLUSIONS: Unlike other glaucomatous patients, FAP patients with glaucoma do not show increased and potentially neuroprotective endocular EPO production in the aqueous humor and may need more aggressive glaucoma management.

Intraocular lens power calculation: angle κ and ocular biomechanics.

PURPOSE: To study the effect of ocular biomechanics on the prediction error of intraocular lens (IOL) power calculation. SETTING: Centro Hospitalar Universitário do Porto, Porto, Portugal. DESIGN: Prospective longitudinal study. METHODS: This study included 67 subjects. Before cataract surgery subjects underwent biometry with IOLMaster 700 and biomechanical analysis with Corvis Scheimpflug technology. The targeted spherical equivalent was calculated with SRK-T and Barrett Universal II. Associations between prediction error (PE), absolute prediction error (AE), and biometric and biomechanical parameters were performed with stepwise multivariate linear correlation analysis. RESULTS: Using the SRKT formula, there was association between PE and Corvis Biomechanical Index (CBI, B = -0.531, P = .011) and between AE and the horizontal offset between the center of the pupil and the visual axis (angle κ, B = -0.274, P = .007). Considering the Barret Universal II formula, PE was independently associated with anterior chamber depth ( B = -0.279, P = .021) and CBI ( B = -0.520, P = .013) and AE was associated with angle κ ( B = -0.370, P = .007). CONCLUSIONS: A large angle κ may reduce the predictability of IOL power calculation. Ocular biomechanics likely influence the refractive outcomes after IOL implantation. This study showed that eyes with softer corneal biomechanics had more myopic PE. This may relate to anteriorization of the effective lens position. Dynamic measurements may be the way to progress into future formulas.

The Visual Impairment of Inherited Retinal Diseases in Portugal as per the National Table of Disabilities.

Purpose: To evaluate the visual impairment of patients with inherited retinal diseases (IRDs), as per the national table of disabilities (TNI). Design: Retrospective, single-center cohort study. Participants: Patients with a clinical diagnosis of IRD were recruited at a referral center in Portugal. Methods: Demographics and clinical data were collected from each individual patient file. The estimated visual disability coefficient was calculated through the evaluation of 7 graduated categories: orbital or eyelid deformities, low vision, visual field change, loss of bi-foveolar fixation, oculomotor palsy, photophobia, and chronic conjunctivitis. The TNI provides minimum and maximum disability values for numerous conditions within each category, which were summed to calculate an overall summary disability coefficient for each patient. Main Outcome Measures: Demographic/clinical and estimated minimum and maximum visual disability coefficient according to the TNI for each patient. Results: This study included 253 patients from 214 families, aged 3 to 80 years, with a mean age of 39.8 ± 20.0 years. The mean estimated minimum and maximum visual disability coefficients as per the TNI were 0.6 ± 0.4 and 0.7 ± 0.4, respectively. The low vision was the single most frequent contributor category (21.7%) present in the calculation of visual impairment. Low vision and visual field changes were the most frequent double combination (18.2%), and the addition of loss of bi-foveolar fixation was the most frequent triple combination (8.3%). Conclusions: This study found that IRD patients had a significant visual disability, with the majority having a disability coefficient ≥0.6, which would qualify them for a "multipurpose disability medical certificate." Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Real-World Experience With Brolucizumab 6 mg for Diabetic Macular Edema.

Background This study aimed to assess functional and anatomical outcomes after one month of treatment with a single intravitreal injection (IVI) of brolucizumab in patients with diabetic macular edema (DME). Methodology A retrospective study was conducted on eyes with DME who received a single IVI of brolucizumab. The study was designed to assess visual function and optical coherence tomography (OCT) biomarkers at baseline and one month following a single brolucizumab IVI. A sub-analysis was conducted between the following two groups: group 1 - treatment with brolucizumab due to burden, needle phobia, or non-compliance (responders to standard anti-vascular endothelial growth factor (VEGF) or naïve); and group 2 - non-responsive to previous therapies (standard anti-VEGF ± corticosteroids). The main outcome measures included best-corrected visual acuity (BCVA; Early Treatment of Diabetic Retinopathy Study (ETDRS) letters), central foveal thickness, and OCT biomarkers such as the presence of subretinal fluid, the number of hyperreflective dots, the disorganization of retinal inner layers, the disruption of outer plexiform layer, external limiting membrane and ellipsoid zone, the presence of cysts in the nuclear layers (outer (ONL) and inner (INL)), and the number of cysts in ONL versus those in the INL. Safety outcomes were assessed. Results A total of 59 eyes from 42 patients were included, of which 47 eyes were in group 1 and 12 eyes were in group 2. At one month, patients had an improvement of two ETDRS letters on BCVA (p = 0.020), lower central foveal thickness (p < 0.001), fewer hyperreflective dots (p = 0.016), less outer plexiform layer disruption (p = 0.004), less inner and outer nuclear layer cysts (p < 0.001 and p = 0.001, respectively) and better relationship between ONL and INL cysts (p = 0.022). Results were significant in the subgroup of patients with previous responsive DME. No adverse events were reported. Conclusions This study demonstrates the effectiveness and safety after one injection of brolucizumab 6 mg in the management of DME, especially in previously responsive DME patients.

Scheimpflug-Based Corneal Biomechanical Analysis As A Predictor of Glaucoma in Eyes With High Myopia.

Purpose: To address if corneal biomechanical behavior has a predictive value for the presence of glaucomatous optical neuropathy in eyes with high myopia. Patients and Methods: This observational cross-sectional study included 209 eyes from 108 consecutive patients, divided into four groups: high myopia and primary open-angle glaucoma (POAG) - HMG, n = 53; high myopia without POAG - HMNG, n = 53; non-myopic with POAG - POAG, n = 50; non-myopic and non-POAG- NMNG, n = 53. Biomechanical assessment was made through a Scheimpflug-camera-based technology. Receiver operating characteristic curves were made for the discrimination between groups. Multivariable logistic regression models were performed to address the predictive value of corneal biomechanics for the presence of glaucoma. Results: Areas Under the Receiver Operating Characteristic (AUROCs) above 0.6 were found in 6 parameters applied to discriminate between HMG and HMNG and six parameters to discriminate between POAG and NMNG. The biomechanical models with the highest power of prediction for the presence of glaucoma included 5 parameters with an AUROC of 0.947 for eyes with high myopia and 6 parameters with an AUROC of 0.857 for non-myopic eyes. In the final model, including all eyes, and adjusted for the presence of high myopia, the highest power of prediction for the presence of glaucoma was achieved including eight biomechanical parameters, with an AUROC of 0.917. Conclusion: Corneal biomechanics demonstrated differences in eyes with glaucoma and mainly in myopic eyes. A biomechanical model based on multivariable logistic regression analysis and adjusted for high myopia was built, with an overall probability of 91.7% for the correct prediction of glaucomatous damage.

The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

Oct biomarkers for early prognosis in diabetic macular edema treatment with ranibizumab.

BACKGROUND: Diabetic macular edema is the main cause of vision loss in patients with diabetic retinopathy. In this work, we aimed to assess the role of Optical Coherence Tomography (OCT) biomarkers in patients treated with ranibizumab. METHODS: A prospective study enrolling 46 eyes with DME under ranibizumab intravitreal therapy with 12 months of follow-up. The primary endpoint was to assess the association between OCT biomarkers at baseline and the type of treatment response. RESULTS: Good responders, compared with partial/non responders, had lower number of inner nuclear layer cysts (INLc) at baseline, (26.5% vs 73.5%, p = 0.035) and presented, at 12 months of follow-up, lower percentage of disorganization of retinal inner layers (12.0% vs 88.0%, p = 0.001), lower disruption of outer plexiform layer (8.7% vs 91.3%, p < 0.001) and lower outer nuclear layer cysts (17.4% vs 82.6%, p = 0.013). At the end of follow-up, it was observed a higher frequency of inner nuclear layer cysts in patients with higher glycated haemoglobin (p = 0.028). CONCLUSION: This study showed the value and importance of OCT parameters, such as absence of INLc, as a prognostic therapeutic response. A normalization of the macular anatomy with ranibizumab is more likely to happen in early complete responders. The association between INLc and higher glycated haemoglobin levels showed the importance of systemic metabolic control in systemic diabetic manifestations. Clinicaltrials.gov NCT04387604.

Monitoring the Patient with Retinal Angiopathy Associated with Hereditary Transthyretin Amyloidosis: Current Perspectives.

Retinal angiopathy associated with hereditary transthyretin amyloidosis (ATTRv), if untreated, may lead to irreversible vision loss. Our purpose was to systematically review the clinical and imaging features of retinal angiopathy associated with ATTRv and assemble a monitoring approach for these patients. All types of original research studies reporting clinical and imaging findings on retinal angiopathy associated with ATTRv were included. The most common clinical findings were tortuous retinal vessels, microaneurysms, retinal hemorrhages, sheathing of retinal vessels, whitish amyloid deposits along retinal arteries, obliteration of retinal vessels, vitreous hemorrhage, retinal and iris neovascularization. The most relevant imaging findings were hyperautofluorescence of perivessel amyloid deposits; delayed arterial filling, vascular leakage, and retinal ischemia on fluorescein angiography; late hypercyanescence along the choroidal arteries on indocyanine green angiography; perivascular hyperreflective material, needle-shaped deposits on the retinal surface and macular edema on optical coherence tomography (OCT) and attenuated retinal vascular network on OCT-angiography. ATTRv patients should be strictly followed to detect and treat retinal angiopathy, avoiding complications. Both panretinal photocoagulation and intravitreal anti-vascular endothelial growth factor have been used to treat retinal angiopathy in ATTRv. In an individual that presents with retinal angiopathy of unknown etiology, ATTRv should be considered as in the differential diagnosis, even out of the initial core countries. The prognostic value of subclinical findings, namely in OCT-A, is not yet established.

Pupillometry: An objective test to assess endocular hereditary transthyretin amyloidosis.

OBJECTIVE: To automatically study the pupillary light reflex in patients with hereditary transthyretin-associated amyloidosis (hATTR). METHODS: Prospective cross-sectional observational study in patients with hATTR with unilateral scalloped iris. Pupillary light reflex of scalloped iris eyes (21 eyes) were compared with non-scalloped iris eyes (21 eyes, paired eyes of the same patients) and also with a control group of 20 healthy eyes, using static and dynamic pupillometry with the Metrovision® MonPack One. RESULTS: No patient presented evident neurological involvment of the cranial nerves. No significant differences were found in the pupillary diameters under standardized lighting conditions (static pupillometry) among groups. In dynamic pupillometry, the amplitude of contraction, the velocity of contraction and the velocity of dilation were statistically significantly lower in eyes with scalloped iris, comparing both with the contralateral non-scalloped iris eyes (p < 0.001 for all) and with eyes from healthy subjects (p < 0.05 for all). CONCLUSION: A scalloped iris reflects a more advanced endocular hATTR and it is associated with an altered pupillary light reflex. Pupillometry may be a quick, simple, and portable test to objectively evaluate ocular amyloid deposition in hATTR eyes. Pupillary light reflex may not be reliable to evaluate neurological dysfunction in these patients.

Ahmed valve for secondary glaucoma in patients with hereditary transthyretin amyloidosis.

OBJECTIVE: To evaluate the surgical outcomes of patients with hereditary transthyretin amyloidosis (TTR-FAP) who underwent Ahmed glaucoma valve (AGV) implantation. METHODS: A retrospective cohort study was performed on patients with a diagnosis of TTR-FAP secondary glaucoma, who underwent AGV implantation in our department, between November 2010 and July 2019. The cumulative probability of treatment success was measured with Kaplan-Meier survival analysis. The primary outcome was success, defined as intraocular pressure (IOP) ≥ 6 mmHg and ≤21 mmHg with or without medication, with no need for further glaucoma surgery and without loss of light perception at last follow-up. Secondary outcomes were postoperative IOP, number of IOP-lowering medications, and rates of complications. RESULTS: The study included 114 eyes of 87 patients. The mean follow-up duration was 3.81 ± 2.11 years (y) [range, 1.00-8.28 y]. Compared to the preoperative values, the mean IOP was reduced from 28.20 ± 7.01 to 12.87 ± 3.76 mmHg at the final visit (p < 0.001), with a reduction in the number of medications from 3.89 ± 0.66 to 1.86 ± 1.43 (p < 0.001). Early and late postoperative complications occurred in 20 (17.09%) and 9 (7.89%) eyes, respectively. Kaplan-Meier analysis indicated probabilities of success of 0.98 at 1 y, 0.97 at 2 y, 0.95 at 3 y, 0.89 at 4 y, 0.77 at 5 y and 0.72 at 6 y. The linear correlation analysis showed a correlation between some characteristics of the natural history of TTR-FAP patients and AGV implantation success. CONCLUSION: Although glaucoma in TTR-FAP patients is very difficult to manage, AGV implantation is an effective and relatively safe procedure.