Genetic profile of syndromic retinitis pigmentosa in Portugal.

PURPOSE: Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal. METHODS: Multicenter, retrospective cohort study. Six Portuguese healthcare providers identified patients with a clinical diagnosis of syndromic RP and available genetic testing results. All patients had been previously subjected to a detailed ophthalmologic examination and clinically oriented genetic testing. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for disease etiology. RESULTS: One hundred and twenty-two patients (53.3% males) from 100 families were included. Usher syndrome was the most frequent diagnosis (62.0%), followed by Bardet-Biedl (19.0%) and Senior-Løken syndromes (7.0%). Deleterious variants were identified in 86/100 families for a diagnostic yield of 86.0% (87.1% for Usher and 94.7% for Bardet-Biedl). A total of 81 genetic variants were identified in 25 different genes, 22 of which are novel. USH2A and MYO7A were responsible for most type II and type I Usher syndrome cases, respectively. BBS1 variants were the cause of Bardet-Biedl syndrome in 52.6% of families. Best-corrected visual acuity (BCVA) records were available at baseline and last visit for 99 patients (198 eyes), with a median follow-up of 62.0 months. The mean BCVA was 56.5 ETDRS letters at baseline (Snellen equivalent ~ 20/80), declining to 44.9 ETDRS letters (Snellen equivalent ~ 20/125) at the last available follow-up (p < 0.001). CONCLUSION: This is the first multicenter study depicting the genetic profile of syndromic RP in Portugal, thus contributing toward a better understanding of this heterogeneous disease group. Usher and Bardet-Biedl syndromes were found to be the most common types of syndromic RP in this large Portuguese cohort. A high diagnostic yield was obtained, highlighting current genetic testing capabilities in providing a molecular diagnosis to most affected individuals. This has major implications in determining disease-related prognosis and providing targeted genetic counseling for syndromic RP patients in Portugal.

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.

Clinical/Demographic Functional Testing and Multimodal Imaging Differences between Genetically Solved and Unsolved Retinitis Pigmentosa.

INTRODUCTION: The purpose of this study was to compare clinical/demographic functional testing and multimodal imaging features between genetically solved and genetically unsolved nonsyndromic retinitis pigmentosa (nsRP) patients. METHODS: A cross-sectional study was conducted at an inherited retinal dystrophies reference center. Consecutive patients with nsRP and available genetic testing results performed between 2018 and 2020 were included. Genetic testing was clinically oriented, and variants were classified according to the American College of Medical Genetics and Genomics. Only class IV or V variants were considered disease-causing. Clinical/demographic, functional, and imaging features were compared between genetically unsolved (G1) and genetically solved (G2) patients. RESULTS: A total of 175 patients (146 families) were included: 68 patients (59 families) in G1 and 107 patients (87 families) in G2. First symptoms <25 years, consanguinity, evidence for a particular inheritance pattern, and the absence of indicators for phenocopies were significantly more prevalent in G2. No significant differences were observed on best-corrected visual acuity. The visual field index and mean central retinal layer thickness were significantly higher in G1. The frequency of atypical features on multimodal imaging did not differ between groups. CONCLUSION: Individual clinical/demographic functional testing and multimodal imaging features should be considered when counseling patients about the probability of identifying disease-causing variants.

Refractive Surgery for Older Children and Adults with Accommodative Esotropia: A Systematic Review.

INTRODUCTION: Accommodative esotropia (AET) is characterized by an esodeviation of the eyes due to uncorrected hyperopia, deficient fusional divergence, or high accommodative convergence. Decreasing hyperopia would reduce accommodative convergence and strabismus. We sought to review the existing evidence regarding the outcomes of refractive surgery in patients with AET. METHODS: A four-database search (Pubmed, ISI Web of Science, Cochrane, and Scopus) was performed from inception to March 2021 using the following MeSH terms: ("Refractive Surgical Procedures" OR "Keratomileusis, Laser In Situ" OR "Photorefractive Keratectomy" OR "Lens Implantation, Intraocular") AND ("Esotropia" OR "Accommodative Esotropia" OR "Refractive Esotropia" OR "Accommodative Strabismus"). No meta-analysis was performed due to studies' heterogeneity. RESULTS: Twenty-eight studies including 22 case series enrolling 378 patients and 6 case reports enrolling 8 patients were selected among 185 original abstracts. In the case series, a total of 378 patients (726 eyes) were recruited with an age range of 8-52 years. All studies reported mean follow-up periods of at least 12 months. Photorefractive keratectomy was performed in 7 studies, laser-assisted in situ keratomileusis in 9 studies, laser-assisted sub-epithelial keratectomy was reported in 1 study, and 3 studies implanted intraocular lenses, including iris-fixated and collamer. Considering the adult patients with a preoperative corrected esodeviation ≤10 prism diopters (PD) (n = 129), all but 5 (3.9%) presented orthophoria or ≤10PD after refractive surgery. All children but 4 (4.5%) ended up with an esodeviation ≤10PD after surgery with those exceptions being in the range of 11-15PD. Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7-34 years and a follow-up range of 4-48 months. Six case reports were included in this review, comprising a total of 8 patients (16 eyes) with an age range of 7-34 years and a follow-up range of 4-48 months. CONCLUSION: Evidence produced so far points out that refractive surgery may be an alternative for spectacle correction for adults with AET ≤10PD. There is not enough evidence to recommend its use for patients under 18 years of age. The safety and predictability of these procedures for this purpose remains unclear as the selection criteria used for these patients are much different than the usual indications and there are no studies with long-term follow-up.

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.

OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY PARAMETERS IN PATIENTS WITH PHACOMATOSIS.

PURPOSE: To compare the retinal vasculature characteristics between eyes of patients with and without phacomatosis. METHODS: Case-control observational study with retinal vasculature evaluation by optical coherence tomography and optical coherence tomography angiography of the macula and disk. RESULTS: The study included 80 eyes. Neurofibromatosis Type 1 patients presented with a higher central macular thickness (P = 0.007), a lower optical disk nervous fiber layer (P = 0.006), a lower perimeter, area, and circularity of the foveal avascular zone (P < 0.05), a higher vascular density of macular avascular layer (AMVD) (P = 0.004), and a lower papillary vascular density of superficial capillary plexus (SPVD) (P = 0.048). Patients with tuberous sclerosis presented with an increase in central macular thickness (P = 0.024) and in vascular densities (P < 0.05) [except for macular vascular density of deep capillary plexus (PMVD), AMVD, and SPVD]. Patients with Sturge-Weber syndrome showed a decrease in optical disk nervous fiber layer (P < 0.001), subfoveal choroid thickness (P = 0.011), macular vascular density of superficial capillary plexus (SMVD) (P = 0.036), and SPVD (P < 0.001). CONCLUSION: Phacomatosis patients showed statistically significant differences of retinal vasculature characteristics, compared to eyes without pathology. Further studies are needed to determine when and if these parameters change with the course of the disease and if they can be used as biomarkers for disease severity or progression.

Retinal Sensitivity and Structural Changes after Focal Photocoagulation for Diabetic Macular Edema: A Multisectorial Comparison.

INTRODUCTION: The hindrance of a macular laser treatment for diabetic macular edema (DME) remains unclear. Our purpose was to evaluate macular functional and structural changes after focal macular photocoagulation for DME. METHODS: This is a prospective cohort study that included patients with mild diabetic retinopathy, submitted to focal macular laser treatment as monotherapy for DME. Patients underwent optical coherence tomography and microperimetry after the necessary number of treatment sessions for complete resolution of DME. Eyes were compared in each macular sector (superior, temporal, and inferior 1- to 3-mm parafoveal ring) according to the presence of laser spots. Relative sensitivity was calculated as sectorial sensitivity divided by general sensitivity. RESULTS: Sixty-four eyes were included. In sectors submitted to focal photocoagulation, we observed a significant reduction in absolute sensitivity (-1.0 to -0.4 dB, depending on the sector analyzed) and relative sensitivity (-2.1 to -0.6%) together with a reduction in the outer nuclear layer (ONL) thickness (-8 to -3 µm). The number of laser spots correlated with both functional and structural changes. CONCLUSION: In macular sectors that underwent photocoagulation, we found a small reduction in retinal sensitivity together with a reduction in the corresponding ONL thickness.

Long-term reproducibility of positive patch test reactions in patients with non-immediate cutaneous adverse drug reactions to antibiotics.

BACKGROUND: As in contact allergy, T cell-mediated hypersensitivity in non-immediate (NI) cutaneous adverse drug reactions (CADRs) to antibiotics is considered to be lifelong, but, in this setting, patch tests have rarely been repeated after long time intervals. OBJECTIVE: To evaluate the long-term reproducibility of positive patch test reactions to antibiotics in patients with NI CADRs. METHODS: Fifty-six patients with NI CADRs to antibiotics who had relevant positive reactions during patch testing were invited to repeat patch tests with a similar antibiotic series 2-15 years thereafter. RESULTS: Twenty patients were included (9 males and 11 females; mean age 54.6 years): 18 with maculopapular exanthema, 1 with drug hypersensitivity syndrome, and 1 with acute generalized exanthematous pustulosis. Results were reproducible in 17 of 20 patients after a mean interval of 6.0 years (range 2-14.7 years). Concerning ß-lactams, 7 of 8 patients remained positive for aminopenicillins, 4 of 4 for isoxazolyl penicillins, and 1 for cefoxitin. Patch test results were also reproducible for clindamycin in 5 of 7 patients, for vancomycin in 1 patient, and for spiramycin in 1 patient. Reproducibility was not affected by the time interval between tests, sex, or age at testing. CONCLUSIONS: In the context of NI CADRs, we showed high reproducibility of positive patch test reactions to various antibiotics, even after several years.

Modified ex-PRESS technique versus Ahmed glaucoma valve as primary glaucoma surgery for hereditary transthyretin amyloidosis glaucoma.

BACKGROUND: To compare the efficacy of modified Ex-PRESS technique (ExP) versus Ahmed Glaucoma Valve (AGV) as primary surgery in hereditary transthyretin amyloidosis (ATTRv) secondary glaucoma. METHODS: Retrospective study at the national amyloidosis centre. Success was defined as an IOP ≥ 6 mmHg and ≤ 21 mmHg with no need for further glaucoma surgery or laser trabeculoplasty and without loss of light perception at the time of the last follow-up. Secondary outcomes included surgical complications, need for hypotensive drugs, and endothelial cell loss. Patients submitted to previous glaucoma surgery were excluded. RESULTS: We included 180 eyes of 150 patients, 121 in AGV and 59 in ExP group. No significant baseline differences were found between groups. At the time of last follow-up, both groups exhibited significant intraocular pressure (IOP) reduction (p < .001) and number of glaucoma medications (p < .001). Kaplan-Meyer analysis showed higher cumulative probability of success for AGV group (80.1% vs. 41.1%, p < .001) and higher mean time to failure (54.5 vs. 36.9 months, respectively, p < 0.001) at 60 months follow-up. AGV showed lower hazard (HR 0.21, 95% CI [0.111-0.407], p < .001) for failure. CONCLUSION: AGV and ExP are safe and effective techniques in the treatment of ATTRv secondary glaucoma. However, AGV's efficacy seems to be more durable.

Corneal Biomechanical Changes in Patients with Inherited Retinal Diseases.

Purpose: Inherited retinal diseases (IRDs) are a group of degenerative disorders of the retina, that can be potentially associated with changes in the anterior segment, but their prevalence and impact are not known. Exploring these concomitant ophthalmologic changes with biomechanical assessment may help identify other non-retina causes of vision loss in these patients, such as corneal ectasia or susceptibility to glaucoma. This study aimed to measure and compare corneal biomechanics in patients with and without IRDs. Methods: A total of 77 patients (154 eyes) with IRD were recruited as the study group. The control group consisted of 77 healthy adults (154 eyes) with matched age and sphere equivalents. All participants underwent a comprehensive assessment including corneal tomography (Pentacam®) and biomechanical assessment (Corvis ST®). A total of 4 second-generation biomechanical parameters and 3 indexes were collected: Ambrosio Relational Thickness (ARTh), Deflection Amplitude Ratio Max (DARM), Integrated Radius (IR) and Stiffness Parameter at Applanation (SP-A1), the final deviation value D of the Belin/Ambrosio Enhanced Ectasia Display (BAD-D), Corvis Biomechanical Index (CBI) and Tomographic Biomechanical Index (TBI). Results: For IRD patients, there was a higher DARM (p < 0.001), lower ARTh (p < 0.001), higher CBI (p < 0.001), higher TBI (p<0.001), and higher BAD-D (p < 0.001) compared to the control group. Regarding discrimination of healthy subjects and IRD patients, ARTh was the most sensitive parameter. Conclusion: The results showed that IRD patients tend to have softer corneal behaviour, compared to eyes without pathology, which may predispose patients to corneal ectasia or glaucoma development. ARTh could be used to screen IRD patients if a non-retina cause of vision loss is suspected.

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.

Brain MRI in patients with V30M hereditary transthyretin amyloidosis.

BACKGROUND: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aß associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. METHODS: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions. RESULTS: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration. CONCLUSIONS: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors.

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.

Current management of inherited retinal degenerations in Portugal (IRD-PT survey).

Inherited retinal dystrophies/degenerations (IRDs) are the leading cause of visual impairment and incurable familial blindness in the Western world. Given the clinical and genetic heterogeneity, establishing a molecular diagnosis is especially relevant. The aim of this study was to perform the first nationwide survey to understand the prevalence and current management of IRDs in Portugal. A response was obtained from 26 healthcare providers (HCP) (76.5% response rate). Only 4 respondents reported not managing IRD patients. Most HCPs (68.1%) reported managing up to 100 patients, while three currently manage between 501 and 1000 patients. Based on the Portuguese population, an estimated IRD prevalence of 0.031%, i.e., about 1 in 3000 individuals, was calculated. In most HCPs (86.3%), most patients are adults, and non-syndromic retinitis pigmentosa is the most frequent diagnosis. Only 4 HCPs currently use the national, web-based IRD registry (IRD-PT). However, all but one respondent expressed interest in participating in such a registry. Genetic testing is available in 54.5%, with 58.3% HCPs reporting solved rates between 61-80%, but 4 to 9 months to get a genetic test result in 83.4% of cases. Based on this survey, the prevalence of biallelic RPE65-associated disease in Portugal is 0.00031%, i.e., approximately 1:300,000 individuals. Data from this study provide vital background information on national differences in the diagnosis and management of IRD patients. Nationwide implementation of the IRD-PT registry should be encouraged and supported to provide population-based reference data and to identify patients eligible for current and future therapies.

Modified Technique of Ex-PRESS® Filtration Device Combined with a Scleral Pocket for Hereditary Transthyretin Amyloidosis (hATTR) Secondary Open-Angle Glaucoma.

Purpose: To evaluate the effectiveness and safety of a modified approach using the Ex-PRESS® implant combined with a scleral pocket in the management of secondary open-angle glaucoma in hereditary transthyretin amyloidosis (hATTR) at our department. Methods: This was a retrospective analysis. The primary endpoints included Intraocular pressure (IOP) evaluation (baseline, 1st day, 1st week, 1, 3, 6, 12 months and at last follow-up) and number of hypotensive drugs (baseline, 6th, 12th months and at last follow-up). As secondary endpoints surgical complications, the need for additional glaucoma surgery and LogMAR BCVA were evaluated. Qualified and complete success were defined as ≥ 30% IOP decrease from baseline, with or without additional medications, respectively. The minimum follow-up was 12 months. Results: A total of 32 eyes were included with a mean follow-up of 2.4±2.9 years. IOP decreased significantly from baseline (27.4±4.4 mmHg) to 1st day (5.00±2.9 mmHg), 1st week (6.9±4.1 mmHg), 1st month (11.7±7.8 mmHg), 3rd month (11.6±6.1 mmHg), 6th month (13.1±6.8 mmHg), 12th month (12.0±3.5 mmHg) and last visit (11.8±2.4 mmHg), p<0.001. There was also a significant reduction in the number of antiglaucoma medications from baseline (3.8±0.6) and last follow-up (0.4±0.8), p<0.001. LogMAR BCVA remained stable (0.25±0.26 at baseline and 0.25±0.24 at last follow-up), p=0.767. Transient hypotony occurred in 17 eyes (53.1%), but only 11 (34.4%) exhibited anterior chamber shallowing and needed additional care, namely cycloplegic drops and viscoelastic injection. Complete surgical success was achieved in 22 eyes (68.8%) and qualified success in 6 eyes (18.8%). Four eyes (12.5%) needed additional glaucoma surgery. Conclusion: The modified ExPRESS® technique appears to be effective, especially when low levels of IOP are required. Additionally, fewer anti-glaucoma drugs were necessary. In the other hand, hypotony was a common side effect with this procedure, although all patients were properly handled, preserving the surgical outcomes.

Comparison of Light-Based Devices in the Treatment of Meibomian Gland Dysfunction.

PURPOSE: To compare different light-based devices, namely, intense pulsed light (IPL) and IPL with low-level light therapy (LLLT), in the treatment of meibomian gland dysfunction (MGD). METHODS: This was a prospective, observational study that included patients with MGD. Group 1 included 58 eyes treated with IPL (eye-light®, Espansione Marketing S.p.A., Bologna, Italy), followed by LLLT (my-mask®, Espansione Marketing S.p.A., Bologna, Italy); Group 2 included 60 eyes treated with IPL (E>Eye®, E-Swin, Houdan, France); and Group 3 included 58 eyes treated with IPL (Thermaeye Plus®, OptiMed, Sydney, Australia). The presence of symptoms (Ocular Surface Disease Index (OSDI)) and ocular surface changes were evaluated at baseline, three weeks, and six months after treatment. RESULTS: At week three, there was an improvement in the OSDI in all groups (p<0.001), without differences among them (p=0.339). The lipid layer thickness (LLT) increased in Groups 1 and 2 (p<0.001), with a similar variation (p=0.144). Patients with superior OSDI and lower LLT at baseline had the greatest improvement in the respective parameters (p<0.001). The basal tear flow increased in Group 1 (p=0.012). Corneal staining (CS) significantly decreased in Groups 2 (p<0.001) and 3 (p<0.001). At six months, compared to three weeks, there was further improvement in the OSDI (p<0.001) and the LLT (p=0.007), in Group 1, and an increase in the presence of CS in Group 3 (p=0.011). CONCLUSION: IPL treatment led to a sustained decrease in patients' symptoms, even after six months. Different IPL devices seem to have different beneficial effects. Adding LLLT to IPL appears to have an additional long-term beneficial effect as well as positive effects on the lacrimal gland.

Ocular Surface Changes in Primary Open Angle Glaucoma Patients Treated With Topical Antihypertensive Drugs.

PRCIS: In this study, patients with glaucoma undergoing topical antihypertensive (TAH) drugs had changes in the ocular surface and more dry eye symptoms than controls. Clinicians should recognize the influence of TAH drops on exacerbating ocular surface disease. PURPOSE: The purpose of this study was to evaluate the ocular surface of eyes with glaucoma treated with TAH drugs. METHODS: Cross-sectional study that included eyes undergoing TAH drugs due to primary open angle glaucoma and controls. The parameters evaluated were: the basal tear flow (basic secretion test); the tear film osmolarity (TearLab); and the noninvasive break-up time, blink score, lipid layer thickness, tear meniscus height, and loss area of the meibomian glands, measured with the IDRA Ocular Surface Analyser. Presence of symptoms [Ocular Surface Disease Index (OSDI)], dry eye disease (DED, TFOS DEWS II criteria), and corneal fluorescein staining were assessed. RESULTS: We included 154 eyes (154 patients), 77 undergoing TAH drugs for glaucoma (group 1) and 77 of controls (group 2). The tear film osmolarity ( P =0.003) and the loss area of the meibomian glands ( P =0.004) were higher in group 1. The noninvasive break-up time ( P =0.005), lipid layer thickness ( P =0.006), and tear meniscus height ( P =0.001) were lower in group 1. The global OSDI score ( P <0.001), the proportion of eyes with severe disease ( P =0.002), according to the OSDI, and with DED ( P <0.001), according to the TFOS DEWS II criteria, were higher in group 1. The proportion of patients with corneal fluorescein staining was higher in group 1 ( P <0.001). There were no significant differences in eyes taking TAH drugs with and without preservatives ( P >0.127). CONCLUSIONS: DED, in patients with glaucoma, is a multifactorial disease, with a strong contribution from TAH drugs. These eyes had changes in almost every measured parameter, translating into the presence of more dry eye symptoms and corneal damage when compared with controls.

RETINAL EMBOLIZATION AFTER CAROTID ECHO DOPPLER: A CASE REPORT.

PURPOSE: To report a case of symptomatic multiple retinal emboli during a carotid Doppler ultrasonography (CDU) procedure. METHODS: Case report documented with clinical records, fundus photography, optical coherence tomography angiography of the retina, and computed tomography angiography of the supraaortic vessels. RESULTS: A 60-year-old male patient presented to the emergency department with sudden vision loss in the left eye and pain in the left upper eyelid noticed during a CDU procedure. On the left eye, the best-corrected visual acuity was 20/200, and fundus observation revealed retinal arteriolar attenuation, retinal whitening with cherry point, and multiple intraarterial emboli in all arcades of the central retinal artery. Computed tomography angiography of the supraaortic vessels revealed an absence of filling throughout the cervical, petrous, and cavernous segment of the left internal carotid artery, resuming only in the ophthalmic segment and an important stenosis of the left external carotid artery. He had no indication to be submitted to left carotid endarterectomy and began ocular massage and oral anticoagulant. Four months later, ptosis was no longer present, best-corrected visual acuity improved to 20/20 with a residual scotoma, and emboli disappeared on fundus photography. CONCLUSION: Embolic occlusion of retinal arteries may be an extremely rare but serious complication associated with CDU, and patients and clinicians should be aware of it.

Long-term results in patients with iris-fixated foldable phakic intraocular lenses for myopia and astigmatism.

PURPOSE: To evaluate the long-term results of iris-fixated foldable phakic intraocular lens (pIOL) implantation for the management of myopia and astigmatism. SETTING: Centro Hospitalar Universitário do Porto, Oporto, Portugal. DESIGN: Prospective clinical study. METHODS: Patients who underwent Artiflex Myopia or Artiflex Toric iris-fixed pIOL implantation for the treatment of myopia or astigmatism between 2003 and 2011 were included. Refractive stability, refractive predictability, safety, efficacy, and cumulative probability of success were evaluated at 5 years, 10 years, and 15 years of follow-up. RESULTS: 5-year, 10-year, and 15-year follow-ups were completed by 199 of 217 (91.7%), 187 of 217 (86.2%), and 43 of 45 (95.6%) eyes implanted with pIOLs, respectively. The mean spherical equivalent was -8.36 ± 2.75 diopters (D), -0.11 ± 0.31 D, -0.33 ± 0.62 D, and -0.80 ± 1.32 D preoperatively and after 5 years, 10 years, and 15 years after surgery. At 5 years, 10 years, and 15 years after surgery, 100%, 95.6%, and 81.6% were within ±1.00 D. The safety and efficacy indexes were 1.07 and 1.06 at 5 years, 1.04 and 0.99 at 10 years, and 1.05 and 1.00 at 15 years of follow-up, respectively. Kaplan-Meier analysis showed survival rates of 97% at 5 years, 73% at 10 years, and 43% at 15 years of follow-up. CONCLUSIONS: Long-term results demonstrated that the implantation of Artiflex pIOLs was a stable, predictable, and effective procedure at 5 years, 10 years, and 15 years of follow-up. Annual follow-up visits to evaluate endothelial cell density and anterior chamber depth decrease, to alert patients to this need in the preoperative evaluation, is recommended.

Pulsed Light Therapy in the Management of Dry Eye Disease: Current Perspectives.

Purpose: To review the indications and efficacy of Intense Pulsed Light (IPL) application in the treatment of Meibomian Gland Dysfunction (MGD). Its main purpose is to describe its physiology, efficacy, indications, and adverse effects. Patients and Methods: A two database (PubMed, EMBASE) search was performed from July 2017 to July 2022 using the MeSH terms ("Intense Pulsed Light" AND ("Meibomian Gland Dysfunction" OR "Dry Eye"). We included randomized studies and systematic reviews with meta-analysis. Exclusion criteria were non-randomized trials, studies enrolling non-MGD dry eye disease, and other works older than 5 years. Results: Current literature shows that IPL is an effective and safe treatment modality for severe dry eye. Available evidence shows improvement of symptoms and objective indicators, such as noninvasive breakup time, thickness of lipid layer, and Schirmer test. However, our review concluded that the beneficial effects of IPL may lose some efficacy at 6-months after the initial session, and subsequent sessions may be required. Thus, IPL treatment should not be considered as first-line therapy for MGD but instead as an adjuvant option to the standard of care. The optimal treatment modality remains unknown and should be tailored according to each patient's phenotype, clinician's experience, and available technology. There is evidence that IPL treatment may down-regulate pro-inflammatory markers (such as interleukin (IL) 6, IL17a, IL-1) and Prostaglandin E2 (PGE2). Conclusion: MGD is a multifactorial disease and IPL treatment seems a promising treatment modality. Despite this, more evidence is needed to study its benefits - since this is an emerging technology, it is expected an increase in comparative studies in the following years, with longer follow-up periods, which may enable more precise conclusions about this treatment modality.