Correlation of the aqueous humor total antioxidant capacity, total oxidant status, and levels of IL-6 and VEGF with diabetic retinopathy status / Correlação entre níveis de humor aquoso da capacidade antioxidante total, estado oxidante total, IL-6, VEGF e status da retinopatia diabética

ABSTRACT Purpose: We aimed to compare the aqueous humor total oxidant status, total antioxidant capacity, and levels of interleukin-6 and vascular endothelial growth factor between patients with diabetic retinopathy and controls and to correlate these levels with the DR status. Methods: Patients who underwent cataract surgery were enrolled. The first group (control group) comprised patients without diabetes; the second group comprised diabetic patients without retinopathy; the third group comprised patients with nonproliferative diabetic retinopathy; and the fourth group comprised patients with proliferative diabetic retinopathy. All patients underwent full ophthalmologic examination before cataract surgery. Prior to surgery, samples of aqueous humor sampling were obtained and stored at -80 °C. Total antioxidant capacity, total oxidant status, and levels interleukin-6 and vascular endothelial growth factor were investigated in these samples and correlated with diabetic retinopathy status. Results: This study analyzed 86 pairs of eyes of 86 patients. All groups were statistically similar in age and sex, but the total antioxidant capacity was lowest in patients with proliferative diabetic retinopathy. Moreover, the total oxidant status and levels of vascular endothelial growth factor and interleukin-6 were found to slightly increase according to the retinopathy status. Conclusion: Oxidative stress, interleukin-6, and vascular endothelial growth factor in the aqueous humor seem to play important roles in the pathogenesis of diabetic retinopathy, especially in the proliferative type.

RESUMO Objetivo: Procurou-se comparar o humor aquoso estado oxidante total, a capacidade antioxidante total, e os níveis de interleucina-6 e do fator de crescimento endotelial vascular entre pacientes com retinopatia diabética e em indivíduos controles, e correlacionar esses níveis com o status da retinopatia diabética. Métodos: Pacientes submetidos à cirurgia de catarata foram incluídos. O primeiro grupo (grupo controle) foi composto por pacientes sem diabetes; o segundo grupo inclui pacientes dia béticos sem retinopatia; o terceiro grupo inclui pacientes com retinopatia diabética não proliferativa; e o quarto grupo inclui pacientes com retinopatia diabética proliferativa. Todos os pacientes foram submetidos a exame oftalmológico completo antes da cirurgia de catarata. Antes da cirurgia, amostras de humor aquoso foram obtidas e armazenadas a -80oC. A capacidade antioxidante total, o estado oxidante total e os níveis de interleucina-6 e fator de crescimento endotelial vascular foram investigados nessas amostras e correlacionados com o status da retinopatia diabética. Resultados: Este estudo analisou 86 pares de olhos de 86 pacientes. Todos os grupos foram estatisticamente semelhantes em idade e sexo, mas a capacidade antioxidante total foi menor em pacientes com retinopatia diabética proliferativa. Além disso, o estado oxidante total e os níveis de fator de crescimento endotelial vascular e interleucina-6 estavam ligeiramente aumentados de acordo com o status da retinopatia. Conclusão: O estresse oxidativo, a interleucina-6 e o fator de crescimento endotelial vascular no humor aquoso parecem desempenhar papel importante na patogênese da retinopatia diabética, especialmente no tipo proliferativo.

Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome / Avaliação dos níveis de renina e angiotensina II na síndrome de pseudo-exfoliação

ABSTRACT Purpose: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. Methods: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. Results: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Conclusion: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

RESUMO Objetivo: A síndrome de pseudo-exfoliação tem sido associada ao comprometimento da função do coração e dos vasos sanguíneos. Foi realizado um estudo para investigar o papel do sistema renina-angiotensina na etiopatogenia da síndrome de pseudo-exfoliação. Métodos: Os sujeitos foram 14 pacientes com síndrome de pseudo-exfoliação e 14 controles saudáveis submetidos à extração de catarata. Amostras pré-operatórias de 5 ml de sangue venoso periférico e humor aquoso perioperatório foram coletadas dos pacientes em ambos os grupos. Os níveis de renina no plasma e humor aquoso foram analisados pelo método imunorradiométrico e os níveis de angiotensina II foram analisados por radioimunoensaio. O SPSS versão 16.0 foi utilizado para análises estatísticas. Considerou-se o valor de p<0,05 para indicar uma diferença estatisticamente significativa. Resultados: A média de idade dos pacientes nos grupos pseudo-exfoliação e controle foi de 71,7 ± 7,1 e 67,4 ± 9,3 anos, respectivamente (p=0,140). O nível médio de renina no humor aquoso foi de 7,73 pg / ml (4,15-21) no grupo controle e 11,95 pg/ml (3,75-18,54) no grupo pseudo-exfoliação (p=0,022). Não houve diferenças entre os dois grupos de renina plasmática, angiotensina II plasmática ou nos níveis de angiotensina II em humor aquoso. As correlações entre os níveis de renina no plasma e no humor aquoso e entre os níveis de angiotensina II no plasma e humor foram examinadas separadamente para cada grupo; n]ao foram observadas correlações significativas no grupo pseudo-exfoliação (r=-0,440, p=0,115; r=-0,414, p=0,142) ou no grupo controle (r=-0,232, p=0,425; r=0,482, p=0,081). Conclusão: Os níveis de renina no humor aquoso são mais elevados na síndrome de pseudo-exfoliação. Os resultados indicam um provável papel do sistema renina-angiotensina na síndrome de pseudo-exfoliação. Novos estudos com maior número de casos são necessários para esclarecer a associação precisa do sistema renina-angiotensina com a etiopatogenia da síndrome de pseudo-exfoliação.

Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats / Efeito anti-inflamatório do licopeno na uveíte induzida por endotoxina em ratos

ABSTRACT Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

RESUMO Objetivo: Avaliamos o efeito do licopeno, um carotenóide dietético e um potente anti-oxidante, sobre a inflamação ocular e estresse oxidativo em modelo de uveíte experimental. Métodos: Uveíte foi induzida por endotoxina (EIU) em ratos Sprague-Dawley por uma única injeção subcutânea de 200 ug de lipopolissacárido (LPS). A indução de EIU foi precedida por injeção intraperitoneal de licopeno em uma dose de 10 mg/kg (grupo LPS + Licopeno) ou veículo de mesmo volume (grupo LPS + Veículo), durante 3 dias consecutivos. O grupo controle positivo recebeu uma dose de 1 mg/kg de Dexametasona (grupo DEX + LPS) e o grupo controle negativo recebeu doses diárias de veículo mas sem LPS (grupo Controle Veículo). Vinte e quatro horas após a administração do LPS, os olhos foram enucleados, humor aquoso foi recolhido, e o número de células infiltrativas, a concentração de proteína, assim como os níveis de óxido nítrico (NO), fator de necrose tumoral α (TNF-α), interleucina-6 e marcadores de estresse oxidativo foram determinados no humor aquoso. Além disso, a resposta inflamatória foi avaliada clinicamente e histologicamente. Resultados: As células infiltrativas, concentração de proteína, o NO, TNF-α, interleucina-6 foram significativamente elevados no humor aquoso de ratos do grupo Grupo LPS + Veículo quando comparados ao Grupo Controle Veículo. O tratamento com licopeno diminuiu significativamente estes aumentos. Comparado ao Grupo LPS + Veículo, o licopeno reduziu significativamente as concentrações no humor aquoso dos marcadores de estresse oxidativo e NO (de 0,29 ± 0,1 μM para 0,19 ± 0,1 μM, p=0,003), o TNF-α (de 71,0 ± 22,3 ng/ml para 50,1 ± 2,1 ng/ml, p=0,043), interleucina-6 (de 121,6 ± 3,0 pg/ml para 111,1 ± 5,6 pg/ml, p=0,008). Do mesmo modo, o aumento do número de células infiltrativas no tecido uveal em seções histológicas foi significativamente inibido pelo licopeno, a pontuação inflamatória diminuiu de 2,0 ± 0,0 para 0,4 ± 0,5, p=0,001. Embora, não tenha sido estatisticamente significativo, o licopeno reduziu a contagem de células infiltrativas e a concentração de proteínas no humor aquoso. Conclusões: Estes resultados sugerem que o licopeno pode ter efeitos benéficos no tratamento da inflamação ocular, através dos seus efeitos anti-inflamatórios e antioxidantes.

Oxidative Stress Levels in Aqueous Humor from High Myopic Patients

PURPOSE: To compare oxidative stress status in the aqueous humor of highly myopic eyes and control eyes. METHODS: Aqueous humor samples were collected from 15 highly myopic eyes (high myopia group) and 23 cataractous eyes (control group) during cataract surgery. Central corneal thickness, corneal endothelial cell density, hexagonality of corneal endothelial cells, and cell area of corneal endothelial cells were measured using specular microscopy. Axial length was measured using ultrasound biometry. 8-Hydroxydeoxyguanosine (8-OHdG) and malondialdehyde levels were measured using enzyme-linked immunosorbent assay. RESULTS: 8-OHdG level was lower in the aqueous humor of myopic patients than in that of control group (p = 0.014) and was positively correlated with central corneal thickness and negatively correlated with axial length (r = 0.511, p = 0.02; r = -0.382, p < 0.001). There was no correlation between 8-OHdG level and corneal endothelial cell density, hexagonality, or cell area. Malondialdehyde level did not show any correlation with any parameters evaluated. CONCLUSIONS: 8-OHdG might be a sensitive biomarker for evaluating oxidative stress status in the eye. Oxidative stress level was lower in the aqueous humor of highly myopic eyes compared to that in control eyes, which indicates lower metabolic activity in these eyes.

Intravitreal Bevacizumab (Avastin) as an Adjuvant for the Treatment of Posterior Scleritis

We report a case of posterior scleritis effectively managed with intravitreal bevacizumab. A 71-year-old woman was diagnosed with posterior scleritis. Although she was initially treated with systemic steroids, her clinical presentation deteriorated. She was then treated with a single intravitreal injection of bevacizumab and aqueous humor collection. The aqueous level of vascular endothelial growth factor prior to the intravitreal injection was 880.51 pg/mL, greater than that in the healthy control group (p < 0.001). One month later, the scleritis was completely resolved, and the patient remained stable during six months of follow-up. Intravitreal bevacizumab appears to be an effective adjuvant therapy for patients with posterior scleritis.

Photoreceptor Disruption Related to Persistent Submacular Fluid after Successful Scleral Buckle Surgery

PURPOSE: To investigate serial changes in photoreceptor status and associated visual outcome in patients with persistent submacular fluid after successful scleral buckle surgery for macula-off rhegmatogenous retinal detachment. METHODS: This was a prospective observational case series including 76 consecutive patients who underwent successful scleral buckle surgery for macula-off rhegmatogenous retinal detachment with symptom duration < or =90 days at a single tertiary hospital. Optical coherence tomography (OCT) and visual acuity examination were performed at one month and three months postoperatively and at three-month intervals until the submacular fluid disappeared. Main outcome measures were postoperative photoreceptor status on OCT and visual acuity. RESULTS: Forty-two patients (55.3%) showed persistent submacular fluid at postoperative one month. Of 42 patients with persistent submacular fluid, three (7.1%) showed photoreceptor disruption on OCT. None of the 34 patients without persistent submacular fluid showed photoreceptor disruption. Two patients (4.8%) had progressive photoreceptor disruption, and one patient (2.4%) had early photoreceptor disruption. All three patients showed photoreceptor reappearance and limited visual restoration after absorption of submacular fluid. Final visual acuities were significantly worse in these three patients (20 / 1000, 20 / 133, and 20 / 133) compared to those of the other patients (mean, 20 / 30) with persistent submacular fluid and intact photoreceptors. CONCLUSIONS: Even after successful scleral buckle surgery for rhegmatogenous retinal detachment, photoreceptor disruption can occur related to persistent submacular fluid and may be a cause of poor visual outcome.

Increased levels of vascular endothelial growth factor in the aqueous humor of patients with diabetic retinopathy.

Purpose: This study aims to investigate the levels of aqueous vascular endothelial growth factor (VEGF) in diabetic patient groups in comparison to normal subjects, and to correlate elevated VEGF with the severity of diabetic retinopathy (DR). Materials and Methods: Aqueous samples were obtained from 78 eyes of 74 patients undergoing intraocular surgery and they were examined by the enzyme-linked immunosorbent assay. Color photographs, optical coherence tomography scans, and fluorescein angiography were used to evaluate patients preoperatively. Results: A strong statistical correlation was found to exist between the level of aqueous VEGF and the severity of DR (P < 0.001), whereas, the VEGF levels in a control group and a diabetic group without DR were not significantly different (P = 0.985). Aqueous VEGF levels were significantly elevated in patients with proliferative DR (PDR) as compared to the control group (P < 0.001), to diabetic patients without retinopathy (NDR) (P < 0.001), and to diabetic patients with nonproliferative DR (NPDR) (P < 0.001). The aqueous VEGF levels were significantly higher in patients with active PDR than in those with quiescent PDR (P = 0.001). On the other hand, a statistically insignificant (P = 0.065) correlation was found between elevated aqueous VEGF and the presence of macular edema in the NPDR group. Conclusions: VEGF was elevated in the aqueous humor of patients with DR compared to that in normal eyes. The aqueous VEGF level had a strong correlation with the severity of retinopathy along with a statistically insignificant difference in macular edema.

Concentration of Vascular Endothelial Growth Factor After Intracameral Bevacizumab Injection in Eyes With Neovascular Glaucoma

PURPOSE: To study the concentration of vascular endothelial growth factor (VEGF) in the aqueous humor before and after intracameral injection of bevacizumab in eyes with neovascular glaucoma, and to detect the duration of an anti-VEGF effect of bevacizumab in the anterior chamber. METHODS: In this prospective interventional case series, 1.25 mg of bevacizumab was injected into the anterior chamber of five eyes in five neovascular glaucoma patients. Aqueous humor samples were obtained just before intracameral injection of bevacizumab and two weeks after injection. The concentrations of VEGF in the aqueous humor were measured using ELISA. To investigate corneal endothelial damage after intrecameral bevacizumab injection, specular microscopy was performed before injection and two weeks after injection. Slit lamp photo and iris fluorescent angiography was performed to determine the regression of iris neovascularization. RESULTS: After injection, substantial regression of neovascularization or fluorescein leakage was seen in all treated eyes. The VEGF concentrations in the aqueous humor in eyes with NVG were 1181.8+/-1248.3 pg/mL before intracameral injection of bevacizumab. Two weeks after injection, the VEGF concentrations decreased to 33.2+/-12.2 pg/mL (p=0.04, Wilcoxon signed rank test). There were no significant changes in IOP or corneal endothelial cells. CONCLUSIONS: Intracameral bevacizumab injection can remarkably reduce iris neovascularization in neovascular glaucoma patients. VEGF levels were significantly decreased two weeks after injection and corneal toxicity was not observed during short term follow-up.

Plasma and aqueous humur ascorbic acid levels in people with cataract from diverse geographical regions of Nepal.

Ascorbic acid in aqueous humor of the eye has a role as an antioxidant in delaying cataract formation. In a cross-sectional comparative study, ascorbic acid levels from aqueous humor and venous blood obtained from patients with cataracts in mountainous regions (1,300-2,000 meters) and subtropical lowlands (<100 meters) of Nepal were measured spectrophotometrically with the objective of comparing the levels of aqueous humor ascorbic acid in patients with cataracts from these two diverse geographical regions. Of 131 patients included in the study, 59 were from the mountainous region of Nepal (Group A) and 72 were from the subtropical lowlands (Group B). The mean (+/- SD) plasma ascorbic acid level (mg%) of the subjects in Group A was 0.65 (+/- 0.20) and Group B was 0.85 (+/- 0.31). The aqueous ascorbic acid levels ranged from 12-28 mg % (mean +/-SD = 17.5+/-4.52) and 14-50 mg % (mean +/-SD =23.47+/-8.66) in Groups A and B, respectively. The difference of the plasma and aqueous humor ascorbic acid levels between the two groups was statistically significant (p<0.01). The plasma and aqueous humor ascorbic acid levels in the people with cataracts from the mountainous region of Nepal were significantly lower than those from subtropical lowlands. This may be because of the effect of high altitude and ultraviolet rays on ascorbic acid metabolism.

Transforming Growth Factor-beta Levels in Human Aqueous Humor of Glaucomatous, Diabetic and Uveitic Eyes

PURPOSE: Transforming growth factor-beta2 is known to be present at elevated levels in the aqueous humor of patients with primary open angle glaucoma (POAG) and diabetes but not in uveitis-related secondary glaucoma. We investigated total TGF-beta2 levels and levels of the active form of TGF-beta2 in the aqueous humor of eyes with different types of glaucoma. METHODS: The concentration of the total and active form of TGF-beta2 was measured in 63 patients with primary open angle glaucoma, neovascular glaucoma complicated with diabetes (NVG), and secondary open angle glaucoma complicated with uveitis (SOAG) using a double antibody 'sandwich-indirect' ELISA method. RESULTS: The levels of total TGF-beta2 in the aqueous samples of POAG, NVG, and SOAG were elevated. The levels of active TGF-beta2 in the aqueous samples of POAG, and NVG were also elevated, whereas the level of active TGF-beta2 was within the normal range in the aqueous samples of SOAG. CONCLUSIONS: These results suggest that the level of TGF-beta2 may play a role in the pathology of various types of glaucoma.

Pharmacokinetics of topically applied sparfloxacin in rabbits.

PURPOSE: Fluoroquinolones are antimicrobial agents that have a broad spectrum of activity and are widely used against many of the ocular pathogens, responsible for conjunctivitis, blepharitis, corneal ulcers etc. The aim of our study was to evaluate the ocular pharmacokinetics of sparfloxacin (0.3% w/v) in the aqueous humour of rabbits. MATERIALS AND METHODS: Pharmacokinetics of topically administered sparfloxacin were determined after a single application of 50 microl topically. The aqueous humour samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, 5 or 6 hours after instillation. High Performance Thin Layer Chromatographic method was used to analyse the drug concentration in the aqueous humour samples. RESULTS: Fifteen minutes after the instillation of 50 microl of sparfloxacin 0.3% solution, the mean concentration in aqueous humour was found to be 1.4 microg/ml, which reaches the peak level of 3.7 microg/ml after 1.3 hours. At 6 hours, the sparfloxacin aqueous levels were 0.562 microg/ml. The clinical efficacy was predicted based on the Maximum Concentration (Cmax): Minimum Inhibitory Concentration (MIC) and Area Under the Concentration-time curve (AUC):MIC ratios. CONCLUSION: The sparfloxacin levels in aqueous humour of rabbits are sufficiently high up to the 6 hours after instillation in the conjunctival sac to provide bactericidal effect against most of the ocular pathogens. Both Cmax:MIC and AUC:MIC ratios are high enough to provide bactericidal effect against most of the ocular pathogens. Sparfloxacin (0.3%) ophthalmic preparation has excellent penetration through cornea.

The Role of Nitric Oxide in Ocular Surface Cells

The role of nitric oxide (NO) in the ocular surface remains unknown. We investigated the conditions leading to an increase of NO generation in tear and the main sources of NO in ocular surface tissue. We evaluated the dual action (cell survival or cell death) of NO depending on its amount. We measured the concentration of nitrite plus nitrate in the tears of ocular surface diseases and examined the main source of nitric oxide synthase (NOS). When cultured human corneal fibroblast were treated with NO producing donor with or without serum, the viabilities of cells was studied. We found that the main sources of NO in ocular surface tissue were corneal epithelium, fibroblast, endothelium, and inflammatory cells. Three forms of NOS (eNOS, bNOS, and iNOS) were expressed in experimentally induced inflammation. In the fibroblast culture system, the NO donor (SNAP, S-nitroso-N-acetyl-D, L-penicillamine) prevented the death of corneal fibroblast cells caused by serum deprivation in a dose dependent manner up to 500 micrometer SNAP, but a higher dose decreased cell viability. This study suggested that NO might act as a doubleedged sword in ocular surface diseases depending on the degree of inflammation related with NO concentration.

Peróxido de hidrógeno en el humor acuoso: 1992-1997 / Hydrogen peroxide in the aqueous humor: 1992-1997

Ideas prevailing in 1991 on hydrogen peroxide in the aqueous humor are outlined. They are critically examined under the light of our finding that the method used to establish aqueous humor levels of peroxide generates itself peroxide during the short time span of the analysis. This is due to the fact that the probe used, dichlorophenol indophenol (DCPIP), spontaneously auto-oxidizes in the presence of oxygen. It was concluded then that the level of hydrogen peroxide in the aqueous humor cannot be higher than about 0.3 microM, the detection limit of the DCPIP method. It was also concluded that the statement commonly made in the literature that aqueous humor hydrogen peroxide derives from the oxidation of ascorbate, an abundant component of that fluid, is based solely on the use of the DCPIP method, and so could easily be due to a methodological artifact. The same applies to the statement that the levels of hydrogen peroxide are very high in human senile cataracts. The surprising resistance to accept the results and conclusions of our 1992 publication is documented. Finally, the content is discussed of an oral presentation made at the 1997 ARVO Annual Meeting in which an important portion of our results and conclusions was confirmed, perhaps signaling a shift towards a wider acceptance of our findings.

Microbiological assay of ampicillin in serum and aqueous humor of patients given ampicillin-sulbactam injection.

The aim of this study was to determine the bacterial growth inhibitory activities of ampicillin in aqueous humor and serum of patients administered ampicillin-sulbactam combination intramuscularly prior to cataract surgery. 43 patients received a combination of both antibiotics intramuscularly at varying periods (60-140 minutes) prior to surgery. Aqueous humor and venous blood were collected at the beginning of the surgery. For microbiological assay, spores of Bacillus subtilis were incorporated in the agar. The test sample and the standard solutions (calibrators) of ampicillin and ampicillin-sulbactam combination were placed in 3 mm wells in the agar. The diameter zones of growth inhibitory activities of ampicillin of the calibrators and the test samples measured in mm were extrapolated to the standard curve and were recorded as ampicillin activity in micrograms/ml. The results of the assay were placed in 5 groups according to the time intervals between injection and collection of serum and aqueous humor (< or = 70, 75, 80, 90, > 90 minutes). Ampicillin activities in sera and aqueous humor of group 5 (> 90 minutes) were significantly higher than the others (p < 0.001). The ratio of ampicillin activities of sera and aqueous humor in group 5 patients was significantly lower indicating higher concentration of ampicillin activity in aqueous humor during this period. Bacterial growth inhibitory activities of ampicillin-sulbactam combination were adequate in aqueous humor of all patients with highest activity being 90 minutes after intramuscular administration indicating the potential usefulness of this antibiotic combination as chemoprophylaxis prior to cataract surgery.

Mecanismos de la secreción del humor acuoso y su modulación por drogas / Aqueous humor secretion mechanisms and it modulation by drugs

Recordemos que el epitelio ciliar consta de dos cepas de células, pigmentadas y no pigmentadas; nuestro concepto es que existe un Sincitium funcional (recordemos que el Sincitium se define como citoplasma con varios núcleos sin límites celulares definidos), esto se refiere a que la membrana basal lateral de las células pigmentadas tiene todos los transportadores que necesita para llevar hacia arriba el cloruro de sodio y luego en consecuencia el agua. Esta membrana tiene el importante intercambio de Na + - K + y obviamente tiene un canal de cloruro y también una etapa de salida de bicarbonato. Nosotros pensamos que esta etapa de salida también puede ser modulada por los inhibidores de la anhidrasa carbónica. Recientemente se mostró en imágenes de video que este concepto es verdadero en el epitelio completo donde ambas cepas de células están juntas; se demostró que los electrolitos son llevados hacia arriba, al interior de la célula, desde las pigmentadas hacia las no pigmentadas y en ellas a la etapa de salida. Por lo tanto hemos visto como el mecanismo del humor acuoso es muy complejo, su secreción comprende apareamiento de transportadores y canales entre células pigmentadas y no pigmentadas y las dos capas de células son funcionalmente una, un Sincitium. Es importante el flujo constante del humor acuoso a través de las cámaras del ojo para una función visual normal. Es necesario un globo ocular formado por una presión intraocular adecuada para mantener la eficacia óptica. Además, el humor acuoso aporta los sustratos necesarios para la función metabólica normal de los tejidos oculares avasculares a los cuales bañan particularmente cristalino, córnea y red trabecular; este flujo de humor acuoso se encarga además de remover los desperdicios metabólicos. Es también un medio para que el iris responda a la luz...

Experimentally designed glaucoma implant surgery with mitomycin C in rabbit

An attempt was made to observe the possibility of controlling intraocular pressure (IOP) without hypotony and ocular motility disorder by installing an experimentally designed glaucoma implant through a small conjunctival incision with the aid of a stylet and maintaining the aqueous reservoir using mitomycin C (MMC). The implant was made of silicone tube, of which one end was occluded by glue and on the same end 4 check-valve-like slits were made. Thirty-five healthy white rabbits were used and subdivided into 4 groups. In groups I to III, implants having 2.0, 2.5, 3.0 mm slit lengths, respectively, were installed with MMC application in one eye of each of the 10 rabbits. In group IV, a 2 mm slit-length implant was installed without MMC in one eye of each of the 5 rabbits. Pneumatonometry and ultrasonography were performed to check the IOP and the formation of aqueous reservoir in the implanted eyes for 8 weeks. In group I through III, there was a statistically significant 4-5 mmHg pressure-lowering effect in the implanted eyes compared to the contralateral control eyes for 8 weeks. The aqueous reservoirs were observed throughout the follow-up period. In group IV, we could observe neither a pressure-lowering effect nor aqueous reservoir formation in the implanted eyes after 2 weeks postoperatively. Hypotony did not occur in implanted eyes in any of the groups. This study shows the possibility of IOP control by installing a specially designed glaucoma implant with application of MMC.