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1.
J Ophthalmic Inflamm Infect ; 13(1): 29, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37294447

RESUMO

BACKGROUND: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. MAIN BODY: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. CONCLUSION: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

2.
J Ophthalmol ; 2022: 3044202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265366

RESUMO

This study tested the protective effect of maslinic acid (MA) against diabetic retinopathy (DR) in rats with type 1 diabetes mellitus (T1DM) and investigated possible mechanisms of action. DM was introduced by streptozotocin (STZ) (65 mg/kg, i.p.). Control and STZ (T1DM) were divided into 2 subgroups, which received either the vehicle or MA (80 mg/kg). Serum, pancreases, and retinas were collected for further use. MA significantly reduced fasting glucose levels in the control and T1DM rats but enhanced fasting insulin levels and partially increased the size of the islets of Langerhans and the number of ß-cells in T1DM rats. In addition, MA significantly improved the retina structure by preventing the reduction in the area between the inner and outer limiting membranes (ILM and OLM, respectively) and increasing the number of cells forming the ganglion cell layer (GCL), inner nuclear layer (INL), and outer nuclear layer (ONL). Associated with these effects, MA significantly reduced the total levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as the nuclear levels of NF-κB p65, mRNA levels of Bax, and protein levels of cleaved caspase-3 in the retinas of T1DM rats. However, MA significantly lowered levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but significantly increased the nuclear levels of Nrf2, protein levels of Bcl2, and total levels of superoxide dismutase (SOD) and reduced glutathione (GSH) in the retinas of the control and T1DM rats. In conclusion, MA prevents DR by antioxidant potential mediated by the activation of Nrf2.

3.
Ophthalmology ; 129(6): 661-667, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35143800

RESUMO

PURPOSE: To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil. DESIGN: Subanalysis of a block-randomized, observer-masked, multicenter clinical trial. PARTICIPANTS: Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017. METHODS: Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group. MAIN OUTCOME MEASURES: Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity. RESULTS: Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 µm and 342 µm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 µm (interquartile range [IQR], -132.3 to 4.0) and 54 µm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 µm (IQR, -32.3 to -0.5) and 50 µm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92). CONCLUSIONS: Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema.


Assuntos
Edema Macular , Uveíte , Antimetabólitos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Humanos , Imunossupressores , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Esteroides/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento , Uveíte/complicações , Uveíte/diagnóstico , Uveíte/tratamento farmacológico
4.
Int Med Case Rep J ; 14: 773-776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815718

RESUMO

BACKGROUND: Central serous chorioretinopathy (CSCR) is an idiopathic condition characterized by serous retinal detachment and/or retinal pigment epithelial (RPE) detachment, the condition associated with a fluid leak through the RPE into subretinal space. This article reports on an unusual case of CSCR following taking adulterated honey mixed with tadalafil powder. CASE PRESENTATION: A 38-year-old male, not known to have any medical illnesses, came to our ophthalmology clinic complaining of sudden onset of blurred central vision in the left eye for five days after taking an adulterated honey which was claimed to improve sexual performance. On taking a history, the patient denied taking any medications or past eye trauma or surgery. On detailed ophthalmologic examination, the best-corrected visual acuity (BCVA) was 20/20 in the right eye and 20/80 in the left eye. Dilated fundus examination of the right eye showed a flat retina, normal macular reflex, healthy optic nerve head and the left eye showed blunt foveal reflex with neurosensory retinal detachment at the macula and subretinal fluid. Optical coherence tomography (OCT) of the left eye showed marked macular thickening, leading to the impression of central serous chorioretinopathy (CSCR). Four weeks after stopping the adulterated honey, BCVA improved to 20/20 in the left eye, with complete resolution of subretinal fluids. CONCLUSION: Our case adds to recently reported cases of a link between tadalafil and CSCR.

5.
Clin Ophthalmol ; 15: 1465-1475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859472

RESUMO

PURPOSE: To study the effects of perioperative uveitis control (PUC) on postoperative intraocular pressure (IOP) and uveitis activity in uveitic glaucoma (UG) patients who required glaucoma surgeries. PATIENTS AND METHODS: A retrospective chart review of 109 patients (120 eyes) which had glaucoma surgery for UG. A total of 66 eyes which had PUC were compared to 54 eyes which did not have. Measurements of IOP and uveitis activity were recorded preoperatively and over 2 years postoperatively. Average number of antiglaucoma medications and frequency of surgical failure were obtained in both groups. RESULTS: Over 2 years postoperatively, average IOP was lower in eyes which had PUC. Significant differences in IOP were found at 3 months (P = 0.004), 6 months (P = 0.001), 1 year (P < 0.001), and 2 years (P < 0.001). Lower grades of anterior chamber (AC) inflammation were found in eyes which had PUC. Significant differences were found at 1 month (P < 0.001), 3 months (P < 0.001) and 6 months (P = 0.001). Mean number of antiglaucoma medications at last visit was 0.7 ± 1.1 for eyes which had PUC and 2.6 ± 1.5 for eyes which did not have PUC (P < 0.001). Among eyes which had PUC, only two eyes required second glaucoma surgeries, while 16 eyes with no PUC required further glaucoma surgeries after 27.7 ± 12.5 months (P < 0.001). CONCLUSION: Proper PUC in patients going for UG surgeries results in lower IOP levels and less AC inflammation over 2 years postoperatively. A comprehensive PUC regimen is needed for uveitic glaucoma patients going for surgeries.

6.
Saudi Med J ; 42(2): 131-145, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33563731

RESUMO

Diabetes mellitus (DM) and its complications are major public health burdens in Saudi Arabia. The prevalence of diabetic retinopathy (DR) is 19.7% and the prevalence of diabetic macular edema (DME) is 5.7% in Saudi Arabia. Diabetic macular edema is a vision-threatening complication of DR and a major cause of vision loss worldwide. Ocular treatments include retinal laser photocoagulation, anti-vascular endothelial growth factor (anti-VEGF) agents, intravitreal corticosteroids, and vitreoretinal surgery when necessary. The present consensus was developed as a part of the Saudi Retina Group's efforts to generate Saudi guidelines and consensus for the management of DME, including recommendations for its diagnosis, treatment, and best practice. The experts' panel stipulates that the treatment algorithm should be categorized according to the presence of central macula involvement. In patients with no central macular involvement, laser photocoagulation is recommended as the first-line option. Patients with central macular involvement and no recent history of cardiovascular (CVS) or cerebrovascular disorders can be offered anti-VEGF agents as the first-line option. In the case of non-responders (defined as an improvement of <20% in optical coherence tomography or a gain of fewer than 5 letters in vision), switching to another anti-VEGF agent or steroids should be considered after 3 injections. Within the class of steroids, dexamethasone implants are recommended as the first choice. In patients with a recent history of CVS events, the use of anti-VEGF agents is not recommended, regardless of their lens status. The experts' panel recommends that a future study be conducted to provide a cut-off point for early switching to steroid implants in pseudo-phakic eyes.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Consenso , Diabetes Mellitus/tratamento farmacológico , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Guias de Prática Clínica como Assunto , Retina , Arábia Saudita , Tomografia de Coerência Óptica , Acuidade Visual
7.
PLoS One ; 15(6): e0233595, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492069

RESUMO

PURPOSE: To assess the one-year effectiveness and safety of ranibizumab 0.5 mg in treatment- naïve patients with diabetic macular edema (DME) enrolled in the real-world LUMINOUS study. PATIENTS AND METHODS: A 5-year, prospective, observational, open-label, global study which recruited 30,138 patients across all approved indications. Consenting patients (≥18 years) who were treatment-naïve or previously treated with ranibizumab or other ocular treatments were treated as per the local ranibizumab label. Here, we present the change in visual acuity (VA) (Early Treatment Diabetic Retinopathy Study letter score; primary treated eye) at Year 1, as well as the change in VA based on injection frequencies (≤4 and ≥5), treatment exposure, and the overall adverse events (AEs) and serious AEs (SAEs) in treatment-naïve DME patients. RESULTS: Of the 4,710 DME patients enrolled in the study, 1,063 were treatment-naïve. At baseline, mean age was 64.5 years, 54.7% were male, and 69.2% were white. At 1 year, mean VA letter score improved by +3.5 (n = 502) from a baseline of 57.7 with a mean of 4.5 injections. Presented by injection frequencies ≤4 and ≥5, VA letter score gains were 0.5 (n = 264) and 6.9 (n = 238) from baseline letter scores of 56.6 and 59.0, respectively. Over 5 years, the incidence of ocular/non-ocular AEs and SAEs was 7.2%/10.1% and 0.3%/5.8%, respectively. No endophthalmitis cases were reported. CONCLUSIONS: The LUMINOUS study included patients with DME with more diverse baseline characteristics than those in randomized clinical trials. The 1-year data showed improvement in VA with low number of injections in treatment- naïve patients with DME. Greater VA gains were observed in patients who received ≥5 injections. No new safety findings were identified. LUMINOUS confirms the effectiveness and safety of ranibizumab for the treatment of patients with DME in a real-world clinical practice.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Edema Macular/complicações , Edema Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos
8.
Middle East Afr J Ophthalmol ; 27(1): 4-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32549717

RESUMO

Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare retinal vasculopathy that might cause subretinal and/or vitreous hemorrhages. Although the primary etiology is still unknown, choroidal neovascularization is mainly involved in the pathogenesis. The main risk factors are age and systemic hypertension. Ancillary testing such as fluorescein angiography, indocyanine green angiography and ultrasonography can be of great value for diagnosing this entity and distinguishing PEHCR from other lesions as choroidal melanoma and retinal vasoproliferative tumor. Various treatments have been reported including photocoagulation, cryotherapy, intravitreal injection of anti-vascular endothelial growth factor (Anti-VEGF) and surgical intervention as pars plana vitrectomy. This review handles an up-to-date perspective regarding PEHCR.


Assuntos
Hemorragia Retiniana/etiologia , Hemorragia Vítrea/etiologia , Inibidores da Angiogênese/uso terapêutico , Corantes/administração & dosagem , Crioterapia , Angiofluoresceinografia , Humanos , Verde de Indocianina/administração & dosagem , Injeções Intravítreas , Fotocoagulação a Laser , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/terapia , Fatores de Risco , Tomografia de Coerência Óptica , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Vitrectomia , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/terapia
9.
Ophthalmic Genet ; 41(4): 394-396, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32429784

RESUMO

PURPOSE: To report a favorable effect of intravitreal dexamethasone implantation in Familial Retinal Arterial Macroaneurysms (FRAM). METHODS: Retrospective Case Report. RESULTS: A 32-year-old male who presented with bilateral retinal macroaneurysms. Whole Exome Sequencing (WES) revealed a homozygous c.830-1 G > A mutation in Insulin Growth Factor Binding Protein 7 (IGFBP7) gene, confirming the diagnosis FRAM. The left eye was lost in the course of the disease, whereas the right eye developed a persistent macular edema due to multiple leaking retinal arterial macroaneurysms and responded poorly to intravitreal ranibizumab and only partially to intravitreal aflibercept. Intravitreal dexamethasone implantation in the right eye, on the other hand, resulted in marked visual and structural improvement. CONCLUSION: Intravitreal dexamethasone injections have beneficial anatomical and visual outcomes in FRAM patients with persistent macular edema poorly responsive to intravitreal injections.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Dexametasona/administração & dosagem , Edema Macular/tratamento farmacológico , Macroaneurisma Arterial Retiniano/tratamento farmacológico , Adulto , Humanos , Injeções Intravítreas , Edema Macular/complicações , Edema Macular/patologia , Masculino , Prognóstico , Macroaneurisma Arterial Retiniano/complicações , Macroaneurisma Arterial Retiniano/patologia , Estudos Retrospectivos , Acuidade Visual
10.
Saudi J Ophthalmol ; 34(2): 136-138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33575539

RESUMO

To describe an unusual case of retinoblastoma in adult Saudi. A 21-year-old Saudi male developed acute unilateral visual loss due to a large intraocular lesion in his left eye. Within five days of presentation, the tumor enlarged rapidly causing angle closure glaucoma and orbital cellulitis like picture. The patient underwent enucleation and the histopathology specimen confirmed the presence of an undifferentiated type tumor cell that was consistent with retinoblastoma with choroidal and optic nerve invasion. Retinoblastoma should be considered in the differential diagnosis of an intraocular mass in adults. To the best of our knowledge, this is the first reported case of an adult presentation of retinoblastoma in Saudi patient.

11.
Graefes Arch Clin Exp Ophthalmol ; 257(9): 1857-1861, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177301

RESUMO

PURPOSE: To evaluate the frequency, etiology, treatment, and visual prognosis of retinal detachment (RD) in patients with uveitis. METHODS: A retrospective review was performed in 707 consecutive patients (1042 eyes) with uveitis, of whom 97 (13.7%) (157 eyes [15.1%]) had RD. RESULTS: There were 126 (12.1%) eyes with exudative retinal detachment (ERD), 16 (1.5%) with tractional retinal detachment (TRD), and 15 (1.4%) with rhegmatogenous retinal detachment (RRD). Panuveitis was most commonly associated with RD (144 (91.1%) eyes). Infectious causes were more common in RRD, and non-infectious etiologies were most common in ERD and TRD. Oral prednisone was the initial therapy in ERD. Additionally, in these cases, cyclosporine was prescribed most frequently (47.1% patients), followed by azathioprine (26.4% patients). Fourteen (87.5%) eyes with TRD and all RRD cases underwent surgery. In patients with ERD, the mean best-corrected visual acuity (BCVA) was 1.1 ± 0.7 LogMAR at baseline and 0.6 ± 0.2 LogMAR at last visit (p = 0.001). In patients with TRD, mean BCVA was 0.7 ± 0.4 LogMAR at baseline and 0.6 ± 0.4 LogMAR at last visit (p = 0.056). In patients with RRD, mean BCVA was 1.6 ± 0.9 LogMAR at baseline and 20 1.3 ± 0.9 LogMAR at last visit (p = 0.185). CONCLUSION: In Saudi Arabia, ERD is observed in 12.1% of the eyes with uveitis, and less than 2% of eyes had TRD or RRD. Visual prognosis is usually good after ERD. Infection is the most frequent cause of RRD associated with uveitis and the visual prognosis is poor.


Assuntos
Previsões , Descolamento Retiniano/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Uveíte/complicações , Acuidade Visual , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Prognóstico , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Inquéritos e Questionários , Uveíte/diagnóstico , Uveíte/epidemiologia , Adulto Jovem
12.
Graefes Arch Clin Exp Ophthalmol ; 257(7): 1353-1364, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30895451

RESUMO

PURPOSE: To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world. METHODS: Non-systematic focused literature review. RESULTS: Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy. CONCLUSIONS: There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.


Assuntos
Angiofluoresceinografia/métodos , Hemoglobinas/metabolismo , Fotocoagulação a Laser/métodos , Retina/diagnóstico por imagem , Doenças Retinianas , Tomografia de Coerência Óptica/métodos , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Fundo de Olho , Saúde Global , Humanos , Prevalência , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Doenças Retinianas/cirurgia
13.
Ocul Immunol Inflamm ; 27(8): 1296-1304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30303435

RESUMO

Purpose: To describe the clinical characteristics and surgical outcomes of panuveitis over a 10-year period.Methods: Data were collected on panuveitis etiology, treatment, surgery and change in vision.Results: Overall, 308 patients (594 eyes) were evaluated, 54.9% with non-granulomatous and 45.1% with granulomatous uveitis. Fifty-four patients had infectious and 254 had non-infectious uveitis. In infectious panuveitis, vision remained unchanged at last visit. The most frequent diagnosis was presumed intraocular tuberculosis (PIOTB) uveitis (48.1%). In the non-infectious subgroup vision increased significantly by 2 lines at last visit (p = 0.020). The most common diagnose was Vogt-Koyanagi-Harada (VKH) disease (38.6%). Initial therapy was oral prednisone in 86.6% with non-infectious etiology followed by immunosuppressive agents. Surgery secondary to complications (mainly cataracts) was performed in 46.7% patients.Conclusion: In Saudi Arabia, panuveitis was mainly due to VHK. PIOTB was the most common etiology for infectious panuveitis. Immunosuppressive therapy and surgery maintained BCVA in non-infectious panuveitis.


Assuntos
Gerenciamento Clínico , Previsões , Pan-Uveíte/terapia , Inquéritos e Questionários , Acuidade Visual , Adolescente , Adulto , Idoso , Criança , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pan-Uveíte/diagnóstico , Pan-Uveíte/epidemiologia , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Tomografia de Coerência Óptica/métodos , Adulto Jovem
14.
Hum Genet ; 135(3): 327-43, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26825853

RESUMO

MERTK is an essential component of the signaling network that controls phagocytosis in retinal pigment epithelium (RPE), the loss of which results in photoreceptor degeneration. Previous proof-of-concept studies have demonstrated the efficacy of gene therapy using human MERTK (hMERTK) packaged into adeno-associated virus (AAV2) in treating RCS rats and mice with MERTK deficiency. The purpose of this study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP). After a preclinical phase confirming the safety of the study vector in monkeys, six patients (aged 14 to 54, mean 33.3 years) with MERTK-related RP and baseline visual acuity (VA) ranging from 20/50 to <20/6400 were entered in a phase I open-label, dose-escalation trial. One eye of each patient (the worse-seeing eye in five subjects) received a submacular injection of the viral vector, first at a dose of 150 µl (5.96 × 10(10)vg; 2 patients) and then 450 µl (17.88 × 10(10)vg; 4 patients). Patients were followed daily for 10 days at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Collected data included (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral domain optical coherence tomography and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects. All patients completed the 2-year follow-up. Subretinal injection of rAAV2-VMD2-hMERTK was associated with acceptable ocular and systemic safety profiles based on 2-year follow-up. None of the patients developed complications that could be attributed to the gene vector with certainty. Postoperatively, one patient developed filamentary keratitis, and two patients developed progressive cataract. Of these two patients, one also developed transient subfoveal fluid after the injection as well as monocular oscillopsia. Two patients developed a rise in AAV antibodies, but neither patient was positive for rAAV vector genomes via PCR. Three patients also displayed measurable improved visual acuity in the treated eye following surgery, although the improvement was lost by 2 years in two of these patients. Gene therapy for MERTK-related RP using careful subretinal injection of rAAV2-VMD2-hMERTK is not associated with major side effects and may result in clinical improvement in a subset of patients.


Assuntos
Terapia Genética/métodos , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Retinose Pigmentar/genética , Retinose Pigmentar/terapia , Adolescente , Adulto , Animais , Dependovirus/genética , Modelos Animais de Doenças , Determinação de Ponto Final , Feminino , Seguimentos , Vetores Genéticos , Humanos , Macaca , Masculino , Pessoa de Meia-Idade , Mutação , Complicações Pós-Operatórias/terapia , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Adulto Jovem , c-Mer Tirosina Quinase
15.
Am J Ophthalmol ; 159(1): 177-84.e1-2, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25448998

RESUMO

PURPOSE: To describe the features of Behçet-associated uveitis over a 25-year period. DESIGN: Retrospective observational case series. METHODS: A chart review of patients with Behçet-associated uveitis who were evaluated from January 1986 to December 2011 at King Khaled Eye Specialist Hospital, Saudi Arabia. Demographic data, symptoms, type of uveitis, treatment, and complications were evaluated. The main outcome measures were presenting symptoms, types of uveitis, treatment, and complications. RESULTS: There were 132 patients (232 eyes; 102 male [77.3%]) evaluated with age of onset of 36.9 ± 11.4 years. Panuveitis was the most common presentation, affecting 118 patients (89.4%). Episodes were bilateral in 100 patients (75.8%). Baseline best-corrected visual acuity (BCVA) was 20/125 in both eyes. Retinal vasculitis at presentation occurred in 61 eyes (26.3%), occlusive vasculitis in 59 eyes (25.4%), and macular edema in 42 eyes (18.1%). Common therapeutic management included oral corticosteroids in 123 patients (93.2%), intravenous steroid therapy in 35 patients (26.5%), cyclosporine in 98 patients (74.2%), and azathioprine in 65 patients (49.2%). Common anterior segment complications included glaucoma (44 eyes, 19%) and cataracts (34 eyes, 14.7%). The most common posterior segment complication was optic nerve atrophy. Cataract surgery was the most common surgery. At last visit, BCVA was better than 20/50 in 131 eyes (56.5%). CONCLUSIONS: Behçet-associated uveitis predominantly affects young men in Saudi Arabia. Bilateral panuveitis associated with retinal vasculitis was the most common manifestation. More than 50% of patients maintained 20/50 or better BCVA at final follow-up and were primarily managed with oral corticosteroids and other immunosuppressive agents.


Assuntos
Síndrome de Behçet/complicações , Uveíte , Corticosteroides/uso terapêutico , Adulto , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Vasculite Retiniana/etiologia , Estudos Retrospectivos , Arábia Saudita , Esteroides/uso terapêutico , Uveíte/etiologia , Uveíte/fisiopatologia , Uveíte/terapia , Acuidade Visual
16.
Br J Ophthalmol ; 98(8): 1101-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24711656

RESUMO

BACKGROUND: Sympathetic ophthalmia is a rare form of bilateral uveitis that develops following an ocular penetrating injury to one eye. Several cases of sympathetic ophthalmia have been reported after non-penetrating cyclodestructive procedures including Nd:YAG and diode laser cyclophotocoagulation (CPC) but information on inciting factors and outcome is limited. In this case series we investigated the inciting factors, clinical features, course and outcome of six patients who developed sympathetic ophthalmia after diode CPC. METHODS: Six patients who developed sympathetic ophthalmia after diode CPC were identified from the King Khaled Eye Specialist Hospital uveitis database between 2008 and 2013. The medical records of these patients were reviewed for demographic information, ocular history, diode laser parameters, clinical presentation, treatment and outcome. RESULTS: Six patients were diagnosed with sympathetic ophthalmia following treatment with diode laser CPC, an incidence of 0.001% during the study period. Two patients had a history of accidental trauma and all patients had undergone at least one ocular surgery that included a variety of procedures. At presentation, two patients had predominantly posterior segment findings in the sympathising eye, one patient had only anterior segment findings and the rest had panuveitis. All patients were treated with topical and systemic corticosteroids and/or immunosupressive therapy that resulted in complete resolution of inflammation and return to baseline vision in the sympathising eye within 2-48 months of treatment. CONCLUSIONS: Sympathetic ophthalmia after diode CPC is rare and is seen in patients with a history of intraocular surgery with or without previous trauma. Early recognition of sympathetic ophthalmia and aggressive management with immunosuppressive therapy results in good outcomes for these patients.


Assuntos
Lasers Semicondutores/efeitos adversos , Fotocoagulação/efeitos adversos , Oftalmia Simpática/etiologia , Adulto , Feminino , Glaucoma/cirurgia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oftalmia Simpática/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
17.
Middle East Afr J Ophthalmol ; 21(1): 40-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24669144

RESUMO

PURPOSE: Listeria monocytogenes is an aerobic, motile, gram positive bacillus recognized as an intercellular pathogen in human where it most frequently affects neonates, pregnant women, elderly patients, and immunosuppressed individuals as well as healthy persons. Ocular listeriosis is rare, most frequently in the form of conjunctivitis, but has been also shown to cause rarely endophthalmitis with pigmented hypopyon and elevated intraocular pressure such as in our case. MATERIALS AND METHODS: We are reporting one immunocompetent patient presenting with dark hypopyon following laser refractive procedure. His clinical findings, investigations, and further management are all described with relevant literature review of similar cases. RESULTS: Diagnosis of ocular listeriosis was confirmed by positive culture of anterior chamber (AC) aspirate with identification of the above organism. His visual outcome was satisfactory with good preserved vision. CONCLUSION: We believe that his ocular infection was exogenous and that ophthalmologists should be aware of the causative organisms of colored hypopyon to avoid delayed diagnosis.


Assuntos
Abscesso/microbiologia , Câmara Anterior/microbiologia , Endoftalmite/microbiologia , Ceratomileuse Assistida por Excimer Laser In Situ , Listeria monocytogenes/isolamento & purificação , Listeriose/microbiologia , Complicações Pós-Operatórias , Abscesso/diagnóstico , Abscesso/tratamento farmacológico , Adulto , Câmara Anterior/patologia , Antibacterianos/uso terapêutico , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Humanos , Implante de Lente Intraocular , Listeriose/diagnóstico , Listeriose/tratamento farmacológico , Masculino , Penicilina G/uso terapêutico , Facoemulsificação
18.
Saudi Med J ; 34(1): 86-90, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23299165

RESUMO

The ocular involvement of tuberculosis is not uncommon but diverse. Rarely, patients initially present with ocular signs that simulate intraocular malignancy. We report 3 cases of isolated presumed choroidal tuberculoma masquerading as intraocular tumor. Two patients had no systemic evidence of tuberculosis with strongly positive purified protein derivative skin test and one patient had evidence of inactive old pulmonary tuberculosis demonstrated by chest computed tomography. Antituberculous regimen including isoniazid 5 mg/kg/day, rifampicin 600 mg/day, ethambutol 15 mg/kg/day, and pyrazinamide 30 mg/kg/day were employed in all cases for 9 months. In addition, oral prednisone 1 mg/kg/day has been given until clinical response was seen, then slowly tapered over 4 months until discontinued. All cases responded well to treatment without complications. Ocular tuberculosis may show challenging clinical presentations, and proper diagnosis and treatment can save the patient's eye and even life.


Assuntos
Neoplasias da Coroide/diagnóstico , Tuberculoma/diagnóstico , Tuberculose Ocular/diagnóstico , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Masculino , Tuberculoma/tratamento farmacológico , Tuberculose Ocular/tratamento farmacológico
19.
Middle East Afr J Ophthalmol ; 19(1): 13-21, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22346110

RESUMO

Sympathetic ophthalmia (SO) is a bilateral diffuse granulomatous intraocular inflammation that occurs in most cases within days or months after surgery or penetrating trauma to one eye. The incidence of SO ranges from 0.2 to 0.5% after penetrating ocular injuries and 0.01% after intraocular surgery. Vitreoretinal surgery and cyclodestructive procedures are considered risk factors. The time from ocular injury to onset of SO varies greatly, ranging from a few days to decades, with 80% of the cases occurring within 3 months after injury to the exciting eye and 90% within 1 year. The diagnosis is based on clinical findings rather than on serological testing or pathological studies. It presents as a bilateral diffuse uveitis. Patients report an insidious onset of blurry vision, pain, epiphora, and photophobia in the sympathizing, non-injured eye. Classically this is accompanied by conjunctival injection and a granulomatous anterior chamber reaction with mutton-fat keratic precipitates (KPs) on the corneal endothelium. In the posterior segment, the extent of inflammation can vary. Systemic corticosteroids are the first line therapy for SO. If patients are non-responsive to steroid therapy or have clinically significant side effects, cyclosporine, azathioprine or other immunosuppressive agents can be used for long-term immunomodulatory therapy.

20.
Can J Ophthalmol ; 46(5): 431-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21995988

RESUMO

OBJECTIVE: Medulloepithelioma is a rare intraocular embryonal neuroepithelial tumour. The study aims at identifying the causes for the delay in diagnosis and treatment. DESIGN: A retrospective study of all cases with histopathologic diagnosis of medulloepithelioma over a period of 25 years. PARTICIPANTS: Six patients with intraocular tumour in 6 eyes. METHODS: A data collection sheet is used for clinical and radiologic information based on charts review. The histologic sections are reviewed by a single pathologist. RESULTS: All cases presented initially in childhood with equal sex distribution. There was a delay of up to 5 years until final diagnosis and management. The most common clinical findings were high intraocular pressure and/or cataract in 4 cases, visible mass/uveitis/iris neovascularization and buphthalmos each presenting in 50% of the patients. The diagnosis was established clinically in 2 cased and by ultrasound in 4 cases. The tumour was mostly malignant (4/6) and 2 cases were classified as teratoid (1 benign and 1 malignant). All patients were successfully treated by enucleation with a follow-up period up to 18 years. CONCLUSIONS: Medulloepithelioma is a rare intraocular tumour often misdiagnosed and treated as glaucoma or uveitis. Ultrasonography is a useful additional tool for diagnosis. Enucleation seems to be an appropriate method of treatment specially when diagnosis is delayed and malignancy is suspected. Ophthalmologists need to be more familiar with this tumour to allow early clinical recognition and diagnosis.


Assuntos
Corpo Ciliar/patologia , Tumores Neuroectodérmicos Primitivos/diagnóstico , Neoplasias Uveais/diagnóstico , Adolescente , Catarata/diagnóstico , Criança , Pré-Escolar , Enucleação Ocular , Feminino , Seguimentos , Humanos , Pressão Intraocular , Masculino , Estudos Retrospectivos
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