Corneal absorption of a new riboflavin-nanostructured system for transepithelial collagen cross-linking.

Corneal collagen cross-linking (CXL) has been described as a promising therapy for keratoconus. According to standard CXL protocol, epithelium should be debrided before treatment to allow penetration of riboflavin into the corneal stroma. However, removal of the epithelium can increase procedure risks. In this study we aim to evaluate stromal penetration of a biocompatible riboflavin-based nanoemulsion system (riboflavin-5-phosphate and riboflavin-base) in rabbit corneas with intact epithelium. Two riboflavin nanoemulsions were developed. Transmittance and absorption coefficient were measured on corneas with intact epithelia after 30, 60, 120, 180, and 240 minutes following exposure to either the nanoemulsions or standard 0.1% or 1% riboflavin-dextran solutions. For the nanoemulsions, the epithelium was removed after measurements to assure that the riboflavin had passed through the hydrophobic epithelium and retained within the stroma. Results were compared to de-epithelialized corneas exposed to 0.1% riboflavin solution and to the same riboflavin nanoemulsions for 30 minutes (standard protocol). Mean transmittance and absorption measured in epithelialized corneas receiving the standard 0.1% riboflavin solution did not reach the levels found on the debrided corneas using the standard technique. Neither increasing the time of exposure nor the concentration of the riboflavin solution from 0.1% to 1% improved riboflavin penetration through the epithelium. When using riboflavin-5-phosphate nanoemulsion for 240 minutes, we found no difference between the mean absorption coefficients to the standard cross-linking protocol (p = 0.54). Riboflavin nanoemulsion was able to penetrate the corneal epithelium, achieving, after 240 minutes, greater stromal concentration when compared to debrided corneas with the standard protocol (p = 0.002). The riboflavin-5-phosphate nanoemulsion diffused better into the stroma than the riboflavin-base nanoemulsion.

Epithelial healing and visual outcomes of patients using omega-3 oral nutritional supplements before and after photorefractive keratectomy: a pilot study.

PURPOSE: To investigate the effect of omega-3 oral nutritional supplementation on corneal reepithelialization, visual acuity, and tear stability after photorefractive keratectomy (PRK). METHODS: This is a prospective, randomized, single-blinded controlled therapeutic trial using omega-3 oral nutritional supplements (TheraTears Nutrition for Dry Eyes; Advanced Vision Research-Akorn, Ann Arbor, MI) conducted at our center. Eighteen healthy patients with refractive error between -1 and -8 diopters were recruited and had bilateral PRK. The treatment group (n = 9 subjects) received omega-3 2 weeks before surgery through 1 month after PRK. The control group (n = 9 subjects) was not given omega-3. Epithelial defects were photographed on postoperative days 0 to 5. Reepithelialization (area in square millimeters) was assessed by fluorescein staining until healing. Tear breakup time (TBUT) and uncorrected distance visual acuity were measured at 1 week, and 1 and 3 months postoperatively. RESULTS: Epithelial defect in the treatment group eyes healed faster compared with that of the controls (P = 0.04). The treatment group eyes healed at an average rate of 1.19% [SD = 0.002; 95% confidence interval (CI), 1.04%-1.34%] per hour, versus 0.83% (SD = 0.0008; 95% CI, 0.77%-0.89%) for controls (Mann-Whitney rank-sum test, P < 0.001). The treatment group eyes maintained a significantly longer TBUT from week 1 through 3 months (mean = 9.52 seconds, SD = 0.81; 95% CI, 8.93-10.10), compared with the controls (mean = 5.52 seconds, SD = 0.81; 95% CI, 4.93-6.10; P < 0.001), and all reached 20/20 vision versus only 4 in the control group 1 month after surgery (P = 0.03). CONCLUSIONS: Omega-3 oral nutritional supplements decreased the average time for epithelial healing, and improved TBUT and visual acuity recovery in PRK. These findings suggested that omega-3 oral nutritional supplementation may be a beneficial adjunct therapy for PRK patients.

Corneal asphericity and spherical aberration after refractive surgery.

PURPOSE: To evaluate changes in corneal asphericity (Q) and spherical aberrations after refractive surgery using Scheimpflug imaging. SETTING: University of California, San Diego, Shiley Eye Center, La Jolla, California, USA. DESIGN: Cohort study. METHODS: After wavefront-guided laser in situ keratomileusis, patients within ± 0.50 diopter of plano and with an uncorrected distance visual acuity of at least 20/20 were evaluated. The Q values and corneal spherical aberration Zernike values were obtained using Scheimpflug imaging preoperatively and 1 to 3 months postoperatively. RESULTS: The study enrolled 177 myopic eyes and 32 hyperopic eyes. The mean Q value was -0.28 ± 0.11 (SD) and -0.22 ± 0.15, respectively, preoperatively and +0.35 ± 0.44 and -0.64 ± 0.31, respectively, postoperatively. The asphericity change was highly correlated with preoperative spherical equivalent (r(2) = 0.81; P ≤ .001). The mean corneal spherical aberration was +0.21 ± 0.08 µm in myopic eyes and +0.36 ± 0.11 µm in hyperopic eyes preoperatively and +0.36 ± 0.17 µm and 0.00 ± 0.29 µm, respectively, postoperatively. The corneal spherical aberration changes were correlated with the amount of preoperative refractive error (r(2) = 0.34; P < .001). There was a tendency for Q values and spherical aberrations to become more positive after myopic ablation and more negative after hyperopic ablation. CONCLUSIONS: Myopic and hyperopic corrections induced changes in the Q value and spherical aberrations in opposite directions (ie, positive and negative, respectively). The changes depended on the magnitude of the refractive correction. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Immunofluorescence confocal microscopy of porcine corneas following collagen cross-linking treatment with riboflavin and ultraviolet A.

PURPOSE: To assess ultrastructural stromal modifications in porcine corneas after riboflavin and ultraviolet A (UVA) exposure using immunofluorescence confocal imaging. METHODS: Twenty-five freshly enucleated porcine eyes were enrolled in the study. Five eyes served as control (group I). Twenty eyes had their epithelium removed (groups I, II, IV, and V) and five eyes had their epithelium intact (group III). Groups II and III were cross-linked with riboflavin 0.1% solution (10 mg riboflavin-5-phosphate in 10 mL 20% dextran-T-500) and exposed to UVA (365 nm, 3 mW/cm2) for 30 minutes. Group IV included five eyes soaked with riboflavin without posterior irradiation, and group V included five eyes irradiated, without previous exposure to riboflavin. Ultra-thin sections (8 microm) of the corneas were stained with anti-collagen I and DAPI and their fluorescence was revealed under confocal microscopy. RESULTS: Only the cross-linked corneas (group II) showed a pronounced, highly organized anterior fluorescence zone of 182.5 +/- 22.5 microm. Using DAPI staining, an anterior and concentrated displacement of cell nuclei due to collagen compaction was observed after crosslinking (group II). No structural changes were observed in all other groups. CONCLUSIONS: The cross-linking treatment effect can be directly visualized using confocal fluorescence imaging, allowing for a quantitative analysis. Cross-linked corneas showed a pronounced and limited anterior zone of organized collagen fibers, which was not observed in the other groups. Treatment of the cornea with riboflavin and UVA without previous deepithelialization did not induce any cross-linking effect. Consequently, to facilitate diffusion of riboflavin throughout the corneal stroma, the epithelium should be removed as an important initial step in the treatment.

Hipertensäo e retinopatia hipertensiva / Hypertension and hypertensive retinopathy

Objetivo: Avaliar a prevalência de retinopatia hipertensiva (RH) em pacientes hipertensos (controlados e näo controlados) e normotensos na populaçäo acima dos 40 anos do município de Piraquara. Correlacionar os casos de alteraçäo retiniana com o sexo, a raça e a idade do paciente. Métodos: Durante 1998 e 2000, foram examinados no Projeto Glaucoma da Universidade Federal do Paraná 1.954 pacientes. Destes, excluíram-se aqueles abaixo de 40 anos e os diabéticos, sendo que a populaçäo considerada para este estudo foi de 1.741 pacientes. O protocolo do projeto consiste de anamnese direcionada, aferiçäo da pressäo arterial (PA), glicemiaportiras reativas, PIO e fundoscopia direta e indireta. As alteraçöes fundoscópicas pertinentes a retinopatia hipertensiva foram estudadas segundo a classificaçäo de Gans e correlacionadas conforme mencionado anteriormente. Resultados: Dos 1.741 pacientes analisados, 669 (38,43 por cento) säo hipertensos, 645 (37,05 por cento) normotensos e 427 (24,53 por cento) suspeitos de hipertensäo arterial sistêmica (HAS). Foram encontrados 211 (12,12 por cento) pacientes com sinais de RH, sendo 136 (64,46 por cento) do sexo feminino e 75 (35,54 por cento) do sexo masculino; 134 (63,98 por cento) de 40 a 60 anos e 77 (36,02 por cento) com idade superior a 60 anos; predominando as raças branca (75,83 por cento) e negra (11,37 por cento). Do total de pacientes com RH, 154 (73 por cento) eram hipertensos, 17 (2,64 por cento) normotensos e 40 (9,37 por cento) suspeitos de HAS. Dentre os hipertensos com PA controlada, 12,2 por cento apresentavam sinais de retinopatia. Já dentre os hipertensos com PA näo controlada, 25,3 por cento apresentavam sinais da patologia. Conclusäo: A prevalência de RH foi maior nos hipertensos comparativamente aos normotensos e suspeitos de HAS (p<0,001, OR=5,32). Os pacientes negros (p<0,05 e OR= 1,67), os hipertensos com PA näo controlada (p<0,01, OR=2,44) e os acima de 60 anos (p<0,001, ORTl,85) apresentaram maiores chances de desenvolverem RH.