VOLUME 87 - ISSUE 5

Purpose: Microperimetry has been used for several years as a form of visual function testing in patients with retinal diseases. Normal microperimetry values obtained with microperimeter MP-3 have not yet been fully published, and baseline values for topographic macular sensitivity and correlations with age and sex are needed to establish degrees of impairment. This study aimed to determine values for light sensitivity thresholds and fixation stability using the MP-3 in healthy individuals.
Methods: Thirty-seven healthy volunteers (age, 28-68 years), underwent full-threshold microperimetry using a 4-2 (fast) staircase strategy with the standard Goldmann III stimulus size and 68 test points positioned identically to those in the Humphrey Field Analyzer 10-2 test grid. The fixation stability was simultaneously recorded during the microperimetry test. The relationship between global sensitivity and age was calculated using linear regression analysis.
Results: Microperimetry was performed on 37 participants (74 eyes). The global mean sensitivity was 29.01 ± 1.44 (range, 26-31) dB. The mean central sensitivity at 2° measured by the MP-3 was 28.5 ± 1.77 dB in the right eye (OD) and 28.75 ± 1.98 dB in the left eye (OS). The total median fixation stability values within 2° and 4° were 80% and 96%, respectively. The linear regression analysis also revealed an age-related global sensitivity decline per year of -0.051 dB ± 0.018 (OD) and -0.078 dB ± 0.021 (OS).
Conclusions: Microperimetry performed with the MP-3 allows for an automatic, accurate, and topography-specific examination of retinal sensitivity thresholds. The results of this study provide a normal and age-matched database of MP-3 microperimetry.

Keywords: Visual fields; Visual field tests; Retina; Microperimetry; Age.

Purpose: This study aimed to compare anterior-chamber parameters acquired by a swept-source anterior-segment optical coherence tomography before and after laser peripheral iridotomy.
Methods: This study prospectively evaluated 14 patients with primary-angle closure and six patients with primary-angle closure glaucoma. Gonioscopy and anterior-segment optical coherence tomography using the DRI OCT Triton^® were performed before and after laser peripheral iridotomy. Anterior-segment optical coherence tomography parameters were studied using scleral spur as reference: angle opening distance at 250, 500, and 750 µm, trabecular-iris space at 500 µm, trabecular-iris angle, trabecular-iris contact length, and iris curvature.
Result: Anterior-segment optical coherence tomography identified 61% of the patients with two or more quadrants closed. Gonioscopy identified more closed angles than anterior-segment optical coherence tomography before laser peripheral iridotomy. In angle parameters, only the angle opening distance of 250 µm at the nasal quadrant was not significantly increased after laser peripheral iridotomy. The iris curvature and trabecular-iris contact length showed a significant reduction induced by the laser procedure. Even in eyes in which gonioscopy did not identify angular widening after laser peripheral iridotomy (n=7), the angle opening distance of 750 µm increased (nasal, 0.15 ± 0.10 mm to 0.27 ± 0.16 mm, p=0.01; temporal, 0.14 ± 0.11 mm to 0.25 ± 0.12 mm, p=0.001) and the iris curvature decreased (nasal, 0.25 ± 0.04 mm vs. 0.11 ± 0.07 mm, p=0.02; temporal, 0.25 ± 0.07 mm vs. 0.14 ± 0.08 mm, p=0.007).
Conclusion: Anterior-chamber changes induced by laser peripheral iridotomy could be quantitatively evaluated and documented by DRI OCT Triton^®.

Keywords: Gonioscopy; Tomography, Optical coherence; Anterior eye segment; Glaucoma, angle-closure; Iridectomy; Laser therapy; Lasers

Purpose: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated.
Methods: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for >6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer’s test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days.
Results: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer’s test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed.
Conclusions: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

Keywords: Dry eye syndromes; Keratoconjunctivitis sicca; Sjögren’s syndrome; Saline solution; Ophthalmic solutions; Methylcellulose

Purpose: Intravitreal antiangiogenic therapy is currently the most invasive ophthalmic procedure performed worldwide. This study aimed to describe the clinical and epidemiological profile of patients undergoing intravitreal antiangiogenic therapy in a tertiary referral hospital in Brazil.
Methods: This cross-sectional, retrospective, and observational study analyzed medical records of patients who received intravitreal injections of antiangiogenic agents for the treatment of retinal diseases at the ophthalmology outpatient clinic in the Hospital das Clínicas at Unicamp between January and December 2020.
Results: The study included 429 patients and 514 eyes. The study population was predominantly male (51.28%), white (80.89%), between 50 and 80 years old (mean age, 60.92 years), had complete or incomplete first-grade education (56.88%), and did not belong to the Regional Health Department of which Campinas is a part (78.55%). Bevacizumab was the most commonly used intravitreal injectable medicine (79.38%), pro re nata was the most commonly used treatment regimen (90.27%), and macular edema was the most prevalent pathology indicative of treatment (60.12%), with diabetes etiology accounting for 48.25%. The average number of injections per patient was 3.83, with the macular neovascularization group and the pro re nata group having the highest and lowest with five and three injections, respectively. Treatment adherence was associated with the patient’s pathology, and the macular edema (52.24%) and macular neovascularization (49.48%) groups had the lowest adherence rates.
Conclusion: This study evaluated the epidemiological and clinical profile of patients undergoing antiangiogenic therapy in a high-complexity public hospital, which is fundamental for a better understanding of the demand for ophthalmic reference service in Brazil, and the analysis of functional results and user adherence profile promotes optimization of indications and leverages the benefits of intravitreal therapy.

Keywords: Retina; Intravitreal injections; Angiogenesis inhibitors; Macular edema; Retinal neovascularization

Purpose: This study aimed to evaluate the classification performance of pretrained convolutional neural network models or architectures using fundus image dataset containing eight disease labels.
Methods: A publicly available ocular disease intelligent recognition database has been used for the diagnosis of eight diseases. This ocular disease intelligent recognition database has a total of 10,000 fundus images from both eyes of 5,000 patients for the following eight diseases: healthy, diabetic retinopathy, glaucoma, cataract, age-related macular degeneration, hypertension, myopia, and others. Ocular disease classification performances were investigated by constructing three pretrained convolutional neural network architectures including VGG16, Inceptionv3, and ResNet50 models with adaptive moment optimizer. These models were implemented in Google Colab, which made the task straight-forward without spending hours installing the environment and supporting libraries. To evaluate the effectiveness of the models, the dataset was divided into 70%, 10%, and 20% for training, validation, and testing, respectively. For each classification, the training images were augmented to 10,000 fundus images.
Results: ResNet50 achieved an accuracy of 97.1%; sensitivity, 78.5%; specificity, 98.5%; and precision, 79.7%, and had the best area under the curve and final score to classify cataract (area under the curve = 0.964, final score = 0.903). By contrast, VGG16 achieved an accuracy of 96.2%; sensitivity, 56.9%; specificity, 99.2%; precision, 84.1%; area under the curve, 0.949; and final score, 0.857.
Conclusions: These results demonstrate the ability of the pretrained convolutional neural network architectures to identify ophthalmological diseases from fundus images. ResNet50 can be a good architecture to solve problems in disease detection and classification of glaucoma, cataract, hypertension, and myopia; Inceptionv3 for age-related macular degeneration, and other disease; and VGG16 for normal and diabetic retinopathy.

Keywords: Neural networks; computer; Deep-learning; Image processing; computer-assisted; VGG16; Inceptionv3; ResNet50; Fundus oculi; Eye diseases.

Purpose: This study aimed to evaluate the pre-sence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the ocular surface of individuals clinically suspected of coronavirus disease 2019 (COVID-19) and determine the accuracy of different approaches of molecular testing on the ocular surface based on the nasopharyngeal positivity status for COVID-19.
Methods: A total of 152 individuals with suspected COVID-19 symptoms who simultaneously underwent nasopharyngeal and two different tear film collection techniques for quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) were included. Tears were collected and randomized: one eye had the filter strip for the Schirmer test and the contralateral eye had conjunctival swab/cytology in the inferior fornix. All patients underwent slit lamp biomicroscopy. The accuracy of various ocular surface collection techniques used for the detection of SARS-CoV-2 RNA was determined.
Results: Of the 152 patients enrolled in the study, 86 (56.6%) had COVID-19 confirmed by nasopharyngeal PCR. Both tear film collection techniques detected viral particles: the Schirmer test was positive in 16.3% (14/86) and the conjunctival swab/cytology in 17.4% (15/86), with no statistically significant differences. No positive ocular tests were found among those with negative nasopharyngeal PCR tests. The overall agreement of the ocular tests was 92.7%, and in combination, the sensitivity would increase to 23.2%. The mean cycle threshold values in the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests were 18.2 ± 5.3, 35.6 ± 1.4, and 36.4 ± 3.9, respectively. Compared with the nasopharyngeal test, the Schirmer (p=0.001) and conjunctival swab/cytology (p<0.001) tests had significantly different Ct values.
Conclusion: The Schirmer (16.3%) and conjunctival swab (17.4%) tests were comparably capable of detecting SARS-CoV-2 RNA in the ocular surface by RT-PCR accurately based on nasopharyngeal status and demonstrated indistinct sensitivity and specificity. Simultaneous specimen sampling and processing from the nasopharyngeal, Schirmer, and conjunctival swab/cytology tests demonstrated significantly lower viral load in both ocular surface approaches than in the nasopharyngeal test. Ocular manifestations detected by slit lamp biomicroscopy were not associated with ocular RT-PCR positivity.

Keywords: COVID-19; SARS-CoV-2; Conjunctiva; Tears; Reverse transcriptase polymerase chain reaction; RNA; viral.

Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma.
Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported.
Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells.
Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

Keywords: Melanoma; Eye neoplasms; Skin neoplasms; Neoplasm metastasis; Vitreous body; Immune checkpoint inhibitors; Immunotherapy; Intravitreal injections; Melphalan; Methotrexate

Purpose: Recently, hyaluronic acid (HA) was proposed as a promising option for the treatment of acquired lower eyelid cicatricial ectropion. However, this effect was not confirmed by quantitative assessments. This study aimed to assess the effect of hyaluronic acid on the treatment of acquired lower eyelid cicatricial ectropion.
Methods: Eight patients with acquired lower eyelid cicatricial ectropion (13 eyelids) were treated with a single 1 mL injection of hyaluronic acid in the preseptal area of the lower eyelid. Evaluation of symptoms and biomicroscopic exam was performed before and 30 days after hyaluronic acid injection. Quantitative analysis of the lower eyelid position (with and without lid traction) was determined before and 30 days after hyaluronic acid injection through standard photographs analyzed using the ImageJ.
Results: All patients experienced partial improvement of symptoms. The lower eyelid position was significantly lifted after hyaluronic acid injection with a significant reduction of medial and lateral angles, reduction of the margin reflex distance, and total and medial ocular fissure area. However, signs of lid margin inflammation and corneal punctate keratitis persisted.
Conclusion: Hyaluronic acid injected in the pre-septal area of the lower eyelid improved acquired lower eyelid cicatricial ectropion symptoms and significantly lifted the position of the lower eyelid. Further studies, with a large number of participants and a long-term follow-up period, are needed to better determine the permanency of the effects of hyaluronic acid injections on the treatment of acquired lower eyelid cicatricial ectropion.

Keywords: Ectropion; Cicatrix; Eyelids; Skin abnormalities; Hyaluronic acid; Dermal fillers; Injections

Purpose: To explore the therapeutic effects of orthokeratology lens combined with 0.01% atropine eye drops on juvenile myopia.
Methods: A total of 340 patients with juvenile myopia (340 eyes) treated from 2018 to December 2020 were divided into the control group (170 cases with 170 eyes, orthokeratology lens) and observation group (170 cases with 170 eyes, orthokeratology lens combined with 0.01% atropine eye drops). The best-corrected distance visual acuity, best-corrected near visual acuity, diopter, axial length, amplitude of accommodation, bright pupil diameter, dark pupil diameter, tear-film lipid layer thickness, and tear break-up time were measured before treatment and after 1 year of treatment. The incidence of adverse reactions was observed.
Results: Compared with the values before treatment, the spherical equivalent degree was significantly improved by 0.22 (0.06, 0.55) D and 0.40 (0.15, 0.72) D in the observation and control groups after the treatment, respectively (p<0.01). After the treatment, the axial length was significantly increased by (0.15 ± 0.12) mm and (0.24 ± 0.11) mm in the observation and control groups, respectively, (p<0.01). After the treatment, the amplitude of accommodation significantly declined in the observation group and was lower than that in the control group, whereas both bright and dark pupil diameters significantly increase and were larger than those in the control group (p<0.01). After the treatment, the tear-film lipid layer thickness and tear break-up time significantly declined in the two groups (p<0.01).
Conclusions: Orthokeratology lens combined with 0.01% atropine eye drops can synergistically enhance the control effect on juvenile myopia with high safety.

Keywords: Atropine; Myopia; Orthokeratologic procedures; Axial length; eye; Corneal topography; Visual acuity; Contact lenses.

Purpose: The regulatory effect of microRNA on diseases has been confirmed. This study aimed to evaluate the expression of microRNA-210-3p in age-related cataracts and assess the effect of abnormal miR-210-3p expressions on H₂O₂-induced SAR01/04 cells.
Methods: Reverse-transcription quantitative polymerase chain reaction method was performed to assess the levels of miR-210-3p in aqueous humor samples. Receiver operating characteristic analysis was employed to assess the discrimination ability of miR-210-3p between patients with age-related cataracts and healthy people, and Pearson correlation analysis was used to identify the correlation between miR-210-3p and oxidative stress indices such as superoxide dismutase, glutathione peroxidase, malonaldehyde. Cell counting kit-8 assay and Transwell assay were used to estimate the biological function of H₂O₂-induced age-related cataract cell model. The levels of oxidative stress indices such as superoxide dismutase, glutathione peroxidase, and malonaldehyde were measured to evaluate the degree of oxidative stress damage in the age-related cataract cell model. The relationship between miR-210-3p and its target gene was verified by luciferase reporter gene analysis.
Results: The miR-210-3p expression was elevated in the aqueous humor of patients with age-related cataracts. A high miR-210-3p expression showed a high diagnostic value for age-related cataracts and was significantly associated with the level of oxidative stress markers in patients with age-related cataracts. The inhibition of miR-210-3p can reverse oxidative stress stimulation and adverse effects on H₂O₂-induced cell function.
Conclusions: The results suggested that miR-210-3p could promote cell viability, cell migration, and oxidative stress by targeting autophagy-related gene 7 in in vitro age-related cataract cell model.

Keywords: Cataract; Age factors; Aqueous humor; MiR-210-3p; Oxidative stress; Autophagy-related protein 7

PURPOSE: To determine and analyze the usability metrics of a free mobile learning app for ophthalmology in Brazil.
METHODS: Metric data from the management dashboard of the CBOQUIZ app were used. All users registered on the platform between March 2019 and June 30, 2021 were included. The number of questions answered, number of correct answers, number of questions answered and correct answers by subject area, and user performance by geographic region were analyzed.
RESULTS: There were 458 active users during the research period and 107,245 questions answered (average, 234.16 questions per user). Of the questions answered, 81,600 (75.5%) were correct and 2,645 were incorrect. The states in Brazil with the best performance were Espírito Santo, Paraiba, and Paraná. The subject area with the lowest hit rate was basic sciences (69.1%), within which embryology demonstrated the lowest hit rate (58.28%). The posterior segment had the highest number of questions answered, followed by miscellaneous topics and the anterior segment. Questions on strabismus were the least answered.
CONCLUSION: The app was used consistently throughout the period studied, and participants adhered to this teaching modality. Performance asymmetry was observed across the Brazil states. The CBOQUIZ app can be used to homogenize ophthalmology teaching in the country.

Keywords: Ophthalmology; Mobile applications; Teaching; Smartphone; Education, distance; Internship and residency; Brazil

PURPOSE: To compare inferomedial wall orbital decompression to balanced medial plus lateral wall orbital decompression in patients with Graves’ orbitopathy in the inactive phase with regard to exophthalmos reduction and the effects on quality of life.
METHODS: Forty-two patients with inactive Graves’ orbitopathy were randomly divided into two groups and submitted to one of two orbital decompression techniques: inferomedial wall orbital decompression or medial plus lateral wall orbital decompression. Preoperative and postoperative assessments included Hertel’s exophthalmometry and a validated Graves’ orbitopathy quality of life questionnaire. The results of the two groups were compared.
RESULTS: Compared to preoperative measurement, exophthalmos reduction was statistically significant in both groups (p<0.001) but more so in patients undergoing medial plus lateral wall orbital decompression (p=0.010). Neither orbital decompression techniques increased the visual functioning subscale score on the Graves’ orbitopathy quality of life questionnaire (inferomedial wall orbital decompression p=0.362 and medial plus lateral wall orbital decompression p=0.727), but a statistically significant difference was observed in the score of the appearance subscale in patients submitted to medial plus lateral wall orbital decompression (p=0.006).
CONCLUSIONS: Inferomedial wall orbital decompression is a good alternative for patients who do not require large exophthalmos reduction. However, medial plus lateral wall orbital decompression offers greater exophthalmos reduction and greater improvement in appearance (higher Graves’ orbitopathy quality of life questionnaire scores), making it a suitable option for esthetic-functional rehabilitation.

Keywords: Graves’ ophthalmopathy; Quality of life; Exophthalmos; Strabismus; Diplopia; Decompression, surgical

This document on myopia control is derived from a compilation of medical literature and the collective clinical expertise of an expert committee comprising members from the Brazilian Society of Pediatric Ophthalmology and the Brazilian Society of Contact Lenses and Cornea. To manage myopia in children, the committee recommends corneal topography and biannual visits with cycloplegic refraction, along with annual optical biometry. For fast-progressing myopia, biannual biometry should be considered. Myopic progression is defined as an annual increase in spherical equivalent greater than 0.50 D/year or in axial length greater than 0.3 mm (until 10 years old) or 0.2 mm (above 11 years). The proposed treatments for myopia progression include environmental control, low concentration atropine, defocus glasses, contact lenses, or Ortho-K lenses, and combinations of these methods may be necessary for uncontrolled cases. Treatment should be sustained for at least 2 years. This document serves as a comprehensive guideline for diagnosing, treating, and monitoring pre-myopic and myopic children in Brazil.

Keywords: Myopia; Pupil disorders; Disease progression; Atropine; Refraction; Ocular; Mydriatics; Contact lens; Biometry; Child; Brazil

The peripherin gene (PRPH2) mutation is associated with photoreceptor cell dysfunction as well as in several inherited retinal dystrophies. The PRPH2 mutation c.582-1G>A is a rare variant reported in retinitis pigmentosa and pattern dystrophy. Here Case 1 was of a 54-year-old woman with bilateral atrophy of the perifoveal retinal pigmentary epithelium and choriocapillaris with central foveolar respect. Autofluorescence and fluorescein angiography revealed perifoveal atrophy of the retinal pigmentary epithelium with an annular window effect without the “dark choroid” sign. Case 2 (mother of Case 1) presented with extensive atrophy of the retinal pigmentary epithelium and choriocapillaris. PRPH2 was evaluated and the c.582-1G>A mutation was identified in heterozygosity. An advanced adult-onset benign concentric annular macular dystrophy diagnosis was thereby proposed. The c.582-1G>A mutation is poorly known and not present in all common genomic databases. This case report is the first one to report a c.582-1G>A mutation associated with benign concentric annular macular dystrophy.

Keywords: PRPH2 gene; Mutation; Macular degeneration; Stargardt disease.

This report presents the optical coherence tomography findings and a new NEU1 mutation in bilateral macular cherry-red spot syndrome associated with sialidosis type 1. A 19-year-old patient with a macular cherry-red spot underwent metabolic and genetic analyses supported by spectral-domain optical coherence tomography. Fundus examination revealed bilateral macular cherry-red spot. Spectral-domain optical coherence tomography revealed increased hyperreflectivity in the retinal inner layers and the photoreceptor layer in the foveal region. The genetic analysis detected a new NEU1 mutation, which caused type I sialidosis. In cases with a macular cherry-red spot, sialidosis should be included in the differential diagnosis, and NEU1 mutation should be screened. Spectral-domain optical coherence tomography alone is not sufficient in the differential diagnosis because childhood metabolic diseases may exhibit similar signs.

Keywords: Mucolipidosis; Myoclonus; Sialidosis type 1; Tomography; optical coherence; Gene NEU1.

A 42-year-old woman presented with bilateral proptosis, chemosis, leg pain, and vision loss. Orbital, chorioretinal, and multi-organ involvement of Erdheim-Chester disease, a rare non-Langerhans histiocytosis, with a negative BRAF mutation was diagnosed based on clinical, radiological, and pathological findings. Interferon-alpha-2a (IFNα-2a) was started, and her clinical condition improved. However, 4 months later, she had vision loss with a history of IFNα-2a cessation. The same therapy was administered, and her clinical condition improved. The Erdheim-Chester disease is a rare chronic histiocytic proliferative disease that requires a multidisciplinary approach and can be fatal if left untreated because of multisystemic involvements.

Keywords: Hemic and lymphatic diseases; Histiocytosis; Histiocytosis, non-Langerhans cell; Erdheim-Chester disease; Retinal diseases; Orbital diseases; Humans; Case reports.