Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study.

PURPOSE: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). DESIGN: Multicenter, observational study. PARTICIPANTS: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384). METHODS: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. MAIN OUTCOME MEASURES: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA). RESULTS: The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. CONCLUSIONS: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.

Evaluation of aflibercept and ziv-aflibercept binding affinity to vascular endothelial growth factor, stability and sterility after compounding.

PURPOSE: To investigate the binding affinity, stability, and sterility of aflibercept and ziv-aflibercept to vascular endothelial growth factor (Holash et al. in Proc Natl Acad Sci USA 99(17):11393-11398, 2002. 10.1073/pnas.172398299) after compounding and storage for up to 28 days at 4 °C and - 8 °C. METHODS: Tuberculin-type 1-mL syringes were prepared containing aflibercept (40 mg/mL) and ziv-aflibercept (25 mg/mL). Samples were stored at 4 °C and - 8 °C for 0, 14, and 28 days and evaluated for the binding affinity of anti-VEGF to VEGF and stability using enzyme-linked immunosorbent assays. The evaluation of sample sterility was performed. RESULTS: Laboratory trials with aflibercept and ziv-aflibercept showed preservation of the drug-binding capability to recombinant VEGF when stored in plastic syringes for up to 28 days at 4 °C and - 8 °C. No significant decrease in mass or concentration were observed. Microbiologic evaluations did not detect contamination in the syringes. CONCLUSIONS: The current study corroborates that compounded anti-VEGF drugs aflibercept and ziv-aflibercept do not loose stability or binding affinity and do not become contaminated if prepared under sterile conditions and stored at 4 °C or - 8 °C for 14 or 28 days.

A novel nonsense mutation in the tyrosinase gene is related to the albinism in a capuchin monkey (Sapajus apella).

BACKGROUND: Oculocutaneous Albinism (OCA) is an autosomal recessive inherited condition that affects the pigmentation of eyes, hair and skin. The OCA phenotype may be caused by mutations in the tyrosinase gene (TYR), which expresses the tyrosinase enzyme and has an important role in the synthesis of melanin pigment. The aim of this study was to identify the genetic mutation responsible for the albinism in a captive capuchin monkey, and to describe the TYR gene of normal phenotype individuals. In addition, we identified the subject's species. RESULTS: A homozygous nonsense mutation was identified in exon 1 of the TYR gene, with the substitution of a cytosine for a thymine nucleotide (C64T) at codon 22, leading to a premature stop codon (R22X) in the albino robust capuchin monkey. The albino and five non-albino robust capuchin monkeys were identified as Sapajus apella, based on phylogenetic analyses, pelage pattern and geographic provenance. One individual was identified as S. macrocephalus. CONCLUSION: We conclude that the point mutation C64T in the TYR gene is responsible for the OCA1 albino phenotype in the capuchin monkey, classified as Sapajus apella.

Choroidal thickness using EDI-OCT in adult-onset vitelliform macular dystrophy.

BACKGROUND: To compare choroidal thickness in patients with adult-onset foveomacular vitelliform dystrophy (AOFVD) with healthy subjects and to correlate choroidal thickness with age, gender and spherical equivalent. METHODS: A prospective, observational study of 37 eyes (15 eyes in AOFVD group and 22 eyes in control group) was conducted. Images were acquired by enhanced depth imaging optical coherence tomography (EDI-OCT). Choroidal thickness measurements were performed in the subfoveal region and at 500, 1000 and 1500 µm intervals from the foveal center to nasal and to temporal regions for subsequent averaging of values. RESULTS: The AOFVD group consisted of four male eyes (28.6 %) and 10 female eyes (71.4 %); age was 33-62 years; spherical equivalent (SE) ranged from -1.50 to 1.50 spherical diopters (SD); mean subfoveal thickness was 325.6 µm, ranging from 186 to 420 µm; and the average of thicknesses was 309.4 µm, ranging from 188 to 413 µm. The control group consisted of 12 male eyes (54.5 %) and 10 female eyes (45.5 %); age was 27-62 years; SE ranged from -2.50 to 0.50 SD; subfoveal thickness was 294.8 µm, ranging from 213 to 481 µm; and the average of thicknesses was 279.4 µm, ranging from 201 to 458 µm. CONCLUSIONS: The AOFVD group and the control group showed similar choroidal thickness by correcting for age, SE and gender. Not yet known, completely, which biochemical and vascular flow alterations of the choroid, and which functional RPE changes may play a role in the pathogenesis of this disease. EDI-OCT, incorporated in some SD-OCT devices, allows higher quality assessment of the choroid. In this article, choroidal thickness of patients with AOFVD, a rare disease with a not fully understood pathogenesis, was assessed.

Combined vitreous and cataract surgeries in highly hyperopic eye.

We report a case of a patient with a highly hyperopic eye who underwent cataract surgery combined with vitreous surgery to create a posterior vitreous detachment (PVD) to prevent choroidal neovascularization (CNV). A 78-year-old man noticed a decrease in his vision due to a cataract in his right eye. The patient had a severe visual loss in his left eye because of a CNV 2 years after a cataract surgery. His visual acuities were 20/30 OD and 20/600 OS, and funduscopic examination showed an orange-colored lesion OD and degenerative subretinal fibrosis OS. The posterior vitreous was attached to the retina in both eyes. The axial length was 18.9 mm OD and 19.0 mm OS. Cataract surgery combined with vitreous surgery to create PVD was performed on the right eye, and the vision improved to 20/20 with no signs of developing CNV after 5 years. We conclude that cataract surgery combined with vitreous surgery to create a PVD may prevent the development of CNV in highly hyperopic eyes.

[Analysis of the transplanted corneas at Santa Casa de São Paulo Eye Bank]. / Análise das córneas do Banco de Olhos da Santa Casa de São Paulo utilizadas em transplantes.

PURPOSE: To identify the donors' profile and evaluate the factors influencing the quality of the donated corneas in Santa Casa Eye Bank, from July, 2000 to January, 2004. METHODS: Data from the charts of 151 patients submitted to penetrating keratoplasty, registered in Santa Casa Eye Bank, from July, 2000 to January 2004 resulted in 180 surgeries. RESULTS: Mean age of the donors was 57.57 +/- 19.74 years old (varied from 9 months to 97 years old) and 54.44% were male. The cause of death was predominantly cardiovascular (50.55%), followed by consumptive diseases (17.77%), trauma (14.44%) and others (17.22%). Considering the quality of the cornea, there was no statistically significant difference among the three main groups of cause of death (p=0.527) and time from death to corneal preservation (p=0.053). There was a statistically significant difference between quality of donated corneas above 61 years old and other ages (p=0.037). CONCLUSION: The most frequent cause of death was cardiovascular, followed by pulmonary diseases and trauma. We could also note that factors inherent to donor like age (>60 years old) predisposed to a worse anatomical quality of the cornea and factors like cause of death and time between death and preservation did not influence the quality of the cornea.

Análise das córneas do Banco de Olhos da Santa Casa de São Paulo utilizadas em transplantes / Analysis of the transplanted corneas at Santa Casa de São Paulo Eye Bank

Objetivo: Traçar o perfil do doador de olhos e avaliar os fatores que influenciam na qualidade das córneas captadas pelo Banco de Olhos da Santa Casa de Misericórdia de São Paulo (SCMSP), no período de junho de 2000 a janeiro de 2004. Métodos: Foram estudados os dados dos prontuários de 151 pacientes submetidos a transplante penetrante de córnea, cadastrados no Banco de Olhos da SCMSP, no período entre junho de 2000 e janeiro de 2004, totalizando 180 operações. Resultados: A média da idade dos doadores foi de 55,57 ± 19,74 anos (variando de 9 meses a 97 anos de idade), sendo 54,44 por cento dos pacientes do sexo masculino. As causas mortis predominantes foram as cardiovasculares, com 50,55 por cento, seguidas das doenças consumptivas 17,77 por cento, traumáticas 14,44 por cento e outras, que somadas representam 17,22 por cento. Em relação à qualidade da córnea, não houve diferença estatística significativa em relação aos quatro grupos causas mortis p=0,527), e o tempo decorrido entre o óbito e a preservação (p=0,053). Houve diferença estatisticamente significativa entre a qualidade das córneas de doadores da faixa etária acima de 61 anos de idade em relação às outras faixas etárias (p= 0,037). Conclusão: As causas mortis mais frequentes foram as cardiovasculares, seguidas das causas pulmonares, outras e traumáticas. Observamos também que entre os fatores inerentes ao doador, a faixa etária acima de 60 anos, predispôs à pior qualidade anatômica das córneas, e fatores como a causa mortis e o tempo decorrido entre o óbito e a preservação, não influenciaram na qualidade das mesmas.

Purpose: To identify the donors' profile and evaluate the factors influencing the quality of the donated corneas in Santa Casa Eye Bank, from July, 2000 to January, 2004. Methods: Data from the charts of 151 patients submitted to penetrating keratoplasty, registered in Santa Casa Eye Bank, from July, 2000 to January 2004 resulted in 180 surgeries. Results: Mean age of the donors was 57.57 ± 19.74 years old (varied from 9 months to 97 years old) and 54.44 percent were male. The cause of death was predominantly cardiovascular (50.55 percent), followed by consumptive diseases (17.77 percent), trauma (14.44 percent) and others (17.22 percent). Considering the quality of the cornea, there was no statistically significant difference among the three main groups of cause of death (p=0.527) and time from death to corneal preservation (p=0.053). There was a statistically significant difference between quality of donated corneas above 61 years old and other ages (p=0.037). Conclusion: The most frequent cause of death was cardiovascular, followed by pulmonary diseases and trauma. We could also note that factors inherent to donor like age (>60 years old) predisposed to a worse anatomical quality of the cornea and factors like cause of death and time between death and preservation did not influence the quality of the cornea.

Mechanism of visual sensations experienced during pars plana vitrectomy under retrobulbar anesthesia.

PURPOSE: To investigate the visual sensations experienced by patients during vitrectomy under retrobulbar anesthesia. METHODS: 30 men and 45 women with a mean age of 65.3 +/- 10.6 years underwent vitrectomy under retrobulbar anesthesia for macular disease. 28 eyes had an idiopathic epiretinal membrane, 13 had an idiopathic macular hole, 32 had macular edema (17 diabetic retinopathy and 15 retinal vein occlusion), and 2 had submacular hemorrhage. 49 patients with nonmacular disease underwent similar vitrectomy procedures and were used for comparison. An interview was conducted with the patient about his/her visual sensations during and within 3 h of the vitrectomy. RESULTS: 70 (93.3%) of the patients reported seeing lights, 53 (70.7%) reported seeing colors, and 48 (64.0%) reported seeing movements or moving objects. Of the patients who reported seeing movements or moving objects, 44 (58.7%) reported seeing surgical instruments, and 5 (6.7%) saw the surgeon's fingers or hands. Patients with macular diseases tended to report more visual sensations than patients with nonmacular diseases. The patients' description and drawings appeared to arise mainly from the shadows cast by the intravitreal objects, and some patients perceived highly accurate details including the movements and color of the objects. CONCLUSIONS: Visual sensations are experienced by approximately 90% of the patients, and there may be a common mechanism by which patients perceive the intravitreal objects that are not focused on by the retina through the eye's optical system.

[Transscleral infrared laser retinal photocoagulation experimental study under low visibility conditions]. / Estudo experimental da aplicação retiniana do laser infravermelho via transescleral sob condições de baixa visibilidade.

PURPOSE: Retinal photocoagulation under poor visualization condition is often required. Transscleral infrared laser can be used as an alternative to regular transpupillary treatment. Based upon retinographic measurements, we proposed to estimate the reproducibility as well as ocular wall permeability rate for this treatment. Our primary goal was to evaluate whether this technique can deliver adequate photocoagulation at predetermined parameters without direct retinal visualization. METHODS: In New Zealand pigmented rabbits, optimal transscleral infrared diode laser settings were administered to the right eye. With the same parameters, transpupillary photocoagulation was repeated in the left eye. Retinographic and clinical examinations were performed immediately and two months later. RESULTS: Ocular wall permeability rate varied between 58.95 and 63.87%. Average permeability using a power of 300 mW (63.14%) was found to be higher than that encountered before its enhancement up to 500 mW (59.11%), (P<0.05). CONCLUSIONS: Setting parameters showed dose-response effect. No retinal hole or retinal detachment was noticed in any rabbit. Transscleral infrared photocoagulation appeared to be a reproducible and secure method in the experimental model.

[Trends in the indications for penetrating keratoplasty]. / Tendência de mudança nas indicações de transplante penetrante de córnea.

PURPOSE: To identify the indications for penetrating keratoplasty at the Department of Ophthalmology of the Santa Casa of São Paulo from January 1996 to December 2005 and to compare them with those from January 1991 to December 1995. METHODS: Charts of patients who had undergone penetrating keratoplasty from January 1996 to December 2006 were retrospectively reviewed. RESULTS: There were 587 keratoplasties done in this period. The average age of patients was 49.6 +/- 21.1 years (range 1 to 91 years). The most common indications were infectious keratitis (17.9%), trauma (16%), pseudophakic bullous keratopathy (14.7%), keratoconus (13.1%), regrafts (12.8%) and herpetic keratitis (6.6%). CONCLUSION: The leading indications for penetrating keratoplasty were infectious keratitis, trauma, bullous keratopathy, herpetic keratitis. There was a decreasing trend in penetrating keratoplasty for keratoconus and regraft during the last 10 years.

Estudo experimental da aplicação retiniana do laser infravermelho via transescleral sob condições de baixa visibilidade / Transscleral infrared laser retinal photocoagulation experimental study under low visibility conditions

OBJETIVOS: Pesquisa experimental, com laser de diodo infravermelho, para estimar a segurança, a reprodutibilidade e a permeabilidade da parede ocular à sua atuação clínica, quando aplicado via transescleral, em condições de baixa visibilidade. MÉTODOS: Submetemos olhos de coelhos pigmentados da raça Nova Zelândia à fotocoagulação retiniana por laser de diodo infravermelho. No olho direito, realizamos fotocoagulação via transescleral sob parâmetros de potência e tempo pré-determinados clinicamente. No olho esquerdo, foram repetidos os mesmos valores da potência e tempo usados no olho direito, desta vez, via transpupilar. Imediatamente e após 2 meses, estudos clínicos baseados na retinografia e histopatológicos foram realizados. RESULTADOS: A permeabilidade da parede ocular, quando da aplicação do laser de diodo infravermelho via transescleral, variou entre 58,95 e 63,87 por cento. A média da permeabilidade da parede ocular a 300 mW (63,14 por cento) mostrou-se significativamente superior àquela da permeabilidade da parede ocular encontrada a 500 mW (59,11 por cento), (P<0,05). CONCLUSÕES: Este estudo sugere a existência da relação dose-resposta em relação aos parâmetros empregados na aplicação do laser de diodo infravermelho via transescleral, com permeabilidade da parede ocular mensurável e reprodutível. Nenhuma rotura, hemorragia ou descolamento da retina ou vítreo foi constatado aos exames subseqüentes às aplicações do laser de diodo infravermelho, o que torna o uso da fotocoagulação via transescleral, no modelo experimental, seguro, mesmo sob condições de baixa visibilidade dos meios.

PURPOSE: Retinal photocoagulation under poor visualization condition is often required. Transscleral infrared laser can be used as an alternative to regular transpupillary treatment. Based upon retinographic measurements, we proposed to estimate the reproducibility as well as ocular wall permeability rate for this treatment. Our primary goal was to evaluate whether this technique can deliver adequate photocoagulation at predetermined parameters without direct retinal visualization. METHODS: In New Zealand pigmented rabbits, optimal transscleral infrared diode laser settings were administered to the right eye. With the same parameters, transpupillary photocoagulation was repeated in the left eye. Retinographic and clinical examinations were performed immediately and two months later. RESULTS: Ocular wall permeability rate varied between 58.95 and 63.87 percent. Average permeability using a power of 300 mW (63.14 percent) was found to be higher than that encountered before its enhancement up to 500 mW (59.11 percent), (P<0.05). CONCLUSIONS: Setting parameters showed dose-response effect. No retinal hole or retinal detachment was noticed in any rabbit. Transscleral infrared photocoagulation appeared to be a reproducible and secure method in the experimental model.

Tendência de mudança nas indicações de transplante penetrante de córnea / Trends in the indications for penetrating keratoplasty

OBJETIVO: Determinar as principais indicações de transplante penetrante de córnea no Departamento de Oftalmologia da Irmandade da Santa Casa de Misericórdia de São Paulo nos pacientes operados no período de janeiro de 1996 a dezembro de 2005 e compará-las com os dados obtidos entre janeiro de 1991 e dezembro de 1995. MÉTODOS: Realizado estudo retrospectivo dos prontuários de pacientes submetidos a transplante penetrante de córnea no período de janeiro de 1996 a dezembro de 2005. Para comparação dos resultados utilizamos o estudo realizado no nosso serviço em 1998. RESULTADOS: Quinhentos e oitenta e sete transplantes penetrantes de córnea foram realizados no período de janeiro de 1996 a dezembro de 2005. A idade média dos pacientes foi de 49,6 anos e variou de 1 a 91 anos. As principais indicações de transplante penetrante de córnea foram ceratite infecciosa (17,9 por cento), trauma (16 por cento), ceratopatia bolhosa do pseudofácico (14,7 por cento), ceratocone (13,1 por cento), reoperação (12,8 por cento) e herpes (6,6 por cento). CONCLUSÃO: Houve aumento nas indicações de transplante penetrante de córnea nos últimos 10 anos nos casos de ceratite infecciosa, trauma, ceratopatia bolhosa do pseudofácico e herpes e diminuição nos de ceratocone e reoperação.

PURPOSE: To identify the indications for penetrating keratoplasty at the Department of Ophthalmology of the Santa Casa of São Paulo from January 1996 to December 2005 and to compare them with those from January 1991 to December 1995. METHODS: Charts of patients who had undergone penetrating keratoplasty from January 1996 to December 2006 were retrospectively reviewed. RESULTS: There were 587 keratoplasties done in this period. The average age of patients was 49.6 ± 21.1 years (range 1 to 91 years). The most common indications were infectious keratitis (17.9 percent), trauma (16 percent), pseudophakic bullous keratopathy (14.7 percent), keratoconus (13.1 percent), regrafts (12.8 percent) and herpetic keratitis (6.6 percent). CONCLUSION: The leading indications for penetrating keratoplasty were infectious keratitis, trauma, bullous keratopathy, herpetic keratitis. There was a decreasing trend in penetrating keratoplasty for keratoconus and regraft during the last 10 years.