The Use of Digital Microscopy to Compare the Thicknesses of Normal Corneas and Ex Vivo Rejected Corneal Grafts with a Focus on the Descemet's Membrane.

OBJECTIVE: To compare the thickness of corneal layers, specifically the Descemet's membrane (DM), in normal corneas and in failed grafts due to rejection (FGRs) using the digital histopathology and to propose a model for the measurement of corneal layers using this method. METHODS: This is a prospective, cross-sectional study performed at the MUHC-McGill University Ocular Pathology & Translational Research Laboratory (McGill University, Montreal, Canada). Histopathological sections of 25 normal human corneas and 40 FGRs were fully digitalized and examined. Inclusion criteria: samples diagnosed as normal corneas or FGRs, from patients older than 18 years of age. Exclusion criteria: histopathological sections without adequate tissue or missing epidemiological information. For each sample, the thicknesses of the epithelium, stroma, and DM were acquired. From a perpendicular plane of reference, two central measurements and two nasal and two temporal peripheral measurements were obtained. RESULTS: There were differences between the normal and FGR groups in the mean central thickness of the epithelium (p < 0.001), the nasal and temporal stromal regions (p < 0.001), and of the DM in the nasal and temporal regions (p < 0.001). Compared with the extremities of the sample (nasal and temporal), the mean thickness of the DM in normal corneas was lower in the central region (p < 0.001), and this difference was not found in the FGR group. CONCLUSIONS: Normal corneas have a thinner epithelium in the central region than the FGR group. In addition, the stroma and DM thicknesses of the nasal and temporal periphery were significantly higher in normal corneas than in those from the FGR group. The digital microscopy protocol applied in this study may be useful for further research studies regarding cornea and other tissues.

Validation of direct method to quantify dexamethasone in human aqueous humor by LC-MS/MS.

AIM: Dexamethasone (Dex) has been used for the treatment of ocular diseases, presenting concentrations up to 150 ng/ml in the biological matrix. Drug sampling has been performed from aqueous humor (AH), which the volume varies from 50 to 200 µl, becoming a challenge for analytical analyses. RESULTS: We developed and validated a direct and sensitive method by LC-MS/MS for Dex measurement in human AH, using water as surrogate matrix to reduce the sample volume applied in some validation assays. With accuracies of 99.6% and precision within 15% in the range of 0.1-150 ng/ml, Dex had an 87-day stability. CONCLUSION: Our method is robust and sensitive enough to be applied in bioequivalence studies with human AH using only 20 µl of biological sample.

Indications and visual outcomes of intrastromal corneal ring segment implantation in a large patient series.

OBJECTIVES:: To describe the indications for and visual outcomes of intrastromal corneal ring segment implantation. METHODS:: A large retrospective case-series chart-review study was conducted using Sorocaba Ophthalmological Hospital medical records. This study included 1222 eyes (1196 patients) that were surgically treated between November 2009 and December 2012. The following preoperative data were collected: age, gender, type of medical care and funding source, surgical technique, best-corrected visual acuity, manifest sphere and cylinder refractive error, maximum and minimum central keratometry, and pachymetry measurements of the cornea at the thinnest point and at the ring channel. The postoperative best-corrected visual acuity and patient satisfaction were also determined. The cases were classified into six groups: four keratoconus groups (severe, advanced, moderate and mild), a pellucid marginal degeneration group and a post-graft irregular astigmatism group. This study was approved by the Brazilian Registry of Clinical Trials (UTN number 1111-1182-6181, TRIAL RBR-6S72RF). RESULTS:: The age (mean±standard deviation) of the patients was 31.0±10.0 years. The most prevalent pathology was keratoconus (1147 eyes, 93.8%). A correlation was found between ectasia severity and medical assistance (p<0.001), and the most serious cases was treated by the Brazilian public health system. No complications were found in a total of 1155 surgeries, and after surgery, 959 patients were satisfied. Among the 164 dissatisfied patients, the majority failed to show improved best-corrected visual acuity. CONCLUSION:: Patients in the public health system underwent surgical intervention for keratoconus later than those with private sources of funding. In the vast majority of operated cases, the patients reported improvements in vision.

Indications and visual outcomes of intrastromal corneal ring segment implantation in a large patient series

OBJECTIVES: To describe the indications for and visual outcomes of intrastromal corneal ring segment implantation. METHODS: A large retrospective case-series chart-review study was conducted using Sorocaba Ophthalmological Hospital medical records. This study included 1222 eyes (1196 patients) that were surgically treated between November 2009 and December 2012. The following preoperative data were collected: age, gender, type of medical care and funding source, surgical technique, best-corrected visual acuity, manifest sphere and cylinder refractive error, maximum and minimum central keratometry, and pachymetry measurements of the cornea at the thinnest point and at the ring channel. The postoperative best-corrected visual acuity and patient satisfaction were also determined. The cases were classified into six groups: four keratoconus groups (severe, advanced, moderate and mild), a pellucid marginal degeneration group and a post-graft irregular astigmatism group. This study was approved by the Brazilian Registry of Clinical Trials (UTN number 1111-1182-6181, TRIAL RBR-6S72RF). RESULTS: The age (mean±standard deviation) of the patients was 31.0±10.0 years. The most prevalent pathology was keratoconus (1147 eyes, 93.8%). A correlation was found between ectasia severity and medical assistance (p<0.001), and the most serious cases was treated by the Brazilian public health system. No complications were found in a total of 1155 surgeries, and after surgery, 959 patients were satisfied. Among the 164 dissatisfied patients, the majority failed to show improved best-corrected visual acuity. CONCLUSION: Patients in the public health system underwent surgical intervention for keratoconus later than those with private sources of funding. In the vast majority of operated cases, the patients reported improvements in vision.

Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. METHODS: This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. RESULTS: After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). CONCLUSIONS: Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma.

Effects of misalignments in the retinal nerve fiber layer thickness measurements with spectral domain optical coherence tomography.

Purpose. To investigate misalignments (MAs) on retinal nerve fiber layer thickness (RNFLT) measurements obtained with Cirrus(©) SD-OCT. Methods. This was a retrospective, observational, cross-sectional study. Twenty-seven healthy and 29 glaucomatous eyes of 56 individuals with one normal exam and another showing MA were included. MAs were defined as an improper alignment of vertical vessels in the en face image. MAs were classified in complete MA (CMA) and partial MA (PMA), according to their site: 1 (superior, outside the measurement ring (MR)), 2 (superior, within MR), 3 (inferior, within MR), and 4 (inferior, outside MR). We compared RNFLT measurements of aligned versus misaligned exams in all 4 sectors, in the superior area (sectors 1 + 2), inferior area (sectors 3 + 4), and within the measurement ring (sectors 2 + 3). Results. RNFLT measurements at 12 clock-hour of eyes with MAs in the superior area (sectors 1 + 2) were significantly lower than those obtained in the same eyes without MAs (P = 0.043). No significant difference was found in other areas (sectors 1 + 2 + 3 + 4, sectors 3 + 4, and sectors 2 + 3). Conclusion. SD-OCT scans with superior MAs may present lower superior RNFLT measurements compared to aligned exams.

Glaucoma Diagnostic Accuracy of Machine Learning Classifiers Using Retinal Nerve Fiber Layer and Optic Nerve Data from SD-OCT.

Purpose. To investigate the diagnostic accuracy of machine learning classifiers (MLCs) using retinal nerve fiber layer (RNFL) and optic nerve (ON) parameters obtained with spectral domain optical coherence tomography (SD-OCT). Methods. Fifty-seven patients with early to moderate primary open angle glaucoma and 46 healthy patients were recruited. All 103 patients underwent a complete ophthalmological examination, achromatic standard automated perimetry, and imaging with SD-OCT. Receiver operating characteristic (ROC) curves were built for RNFL and ON parameters. Ten MLCs were tested. Areas under ROC curves (aROCs) obtained for each SD-OCT parameter and MLC were compared. Results. The mean age was 56.5 ± 8.9 years for healthy individuals and 59.9 ± 9.0 years for glaucoma patients (P = 0.054). Mean deviation values were -1.4 dB for healthy individuals and -4.0 dB for glaucoma patients (P < 0.001). SD-OCT parameters with the greatest aROCs were cup/disc area ratio (0.846) and average cup/disc (0.843). aROCs obtained with classifiers varied from 0.687 (CTREE) to 0.877 (RAN). The aROC obtained with RAN (0.877) was not significantly different from the aROC obtained with the best single SD-OCT parameter (0.846) (P = 0.542). Conclusion. MLCs showed good accuracy but did not improve the sensitivity and specificity of SD-OCT for the diagnosis of glaucoma.

Topiramate-associated acute, bilateral, angle-closure glaucoma: case report.

This paper describes a topiramate induced acute bilateral angle-closure glaucoma. This rare adverse effect is an idiosyncratic reaction characterized by uveal effusion and lens forward displacement, leading to increased intraocular pressure and vision loss. We describe a 55 year-old white woman with migraine, spasmodic torticollis and essential tremor, who developed bilateral acute angle-closure glaucoma, one week after starting topiramate 25 mg/day. She was seen at the Ophthalmology Emergency Department of the Fundação João Penido Burnier (Campinas, SP, Brazil) with a 4 hours history of blurry vision, ocular pain and bright flashes vision. Slit lamp examination revealed moderate conjunctival injection and corneal edema, and shallow anterior chambers. Intraocular pressure was 48 mmHg in both eyes. Fundoscopic examination findings were normal. She was treated with timolol, brimonidine, dorzolamide, pilocarpine, prednisone acetate eye drops and acetazolamide. One hour after those measures, as the intraocular pressure was 30 mmHg, she received a manitol intravenous injection and the intraocular pressure normalized. After 24 hours an iridotomy with Yag laser was performed. Topiramate was discontinued and she was totally recovered after one week.

Topiramate-associated acute, bilateral, angle-closure glaucoma: case report / Glaucoma agudo de ângulo fechado, bilateral, desencadeado pelo topiramato: relato de caso

This paper describes a topiramate induced acute bilateral angle-closure glaucoma. This rare adverse effect is an idiosyncratic reaction characterized by uveal effusion and lens forward displacement, leading to increased intraocular pressure and vision loss. We describe a 55 year-old white woman with migraine, spasmodic torticollis and essential tremor, who developed bilateral acute angle-closure glaucoma, one week after starting topiramate 25 mg/day. She was seen at the Ophthalmology Emergency Department of the Fundação João Penido Burnier (Campinas, SP, Brazil) with a 4 hours history of blurry vision, ocular pain and bright flashes vision. Slit lamp examination revealed moderate conjunctival injection and corneal edema, and shallow anterior chambers. Intraocular pressure was 48 mmHg in both eyes. Fundoscopic examination findings were normal. She was treated with timolol, brimonidine, dorzolamide, pilocarpine, prednisone acetate eye drops and acetazolamide. One hour after those measures, as the intraocular pressure was 30 mmHg, she received a manitol intravenous injection and the intraocular pressure normalized. After 24 hours an iridotomy with Yag laser was performed. Topiramate was discontinued and she was totally recovered after one week.

Relato de um caso de glaucoma bilateral de ângulo fechado induzido pelo topiramato. Este raro efeito colateral é uma idiosincrasia causada por efusão uveal e deslocamento do cristalino para frente, causando aumento da pressão intraocular e perda visual. Descrevemos o caso de uma paciente de 55 anos com migrânea, torcicolo espasmódico e tremor essencial, que desenvolveu glaucoma bilateral de ângulo fechado uma semana após iniciar o uso de topiramato, 25 mg/dia. A paciente foi atendida no setor de Emergências Oftalmológicas da Fundação Penido Burnier (Campinas, SP, Brasil), com história de 4 horas de embaçamento visual, dor ocular e visão de flashes brilhantes. O exame com lâmpada de fenda revelou injeção conjuntival moderada, edema corneano e câmara anterior rasa em ambos os olhos. A pressão intraocular era de 48 mmHg bilateralmente e a fundoscopia era normal. Foi tratada com colírios de timolol, brimonidina, dorzolamida, pilocarpina e acetato de prednisona e acetazolamida via oral. Uma hora após essas medidas, a pressão intraocular era 30 mmHg, e a paciente recebeu uma injeção intravenosa de manitol, ocorrendo normalização da pressão intraocular após essa medida. Após 24 horas foi realizada iridectomia com Yag laser. O topiramato foi interrompido e ela se recuperou totalmente após uma semana.