Light-Modulated Sunscreen Mechanism in the Retina of the Human Eye.

The functioning of the human eye in the extreme range of light intensity requires a combination of the high sensitivity of photoreceptors with their photostability. Here, we identify a regulatory mechanism based on dynamic modulation of light absorption by xanthophylls in the retina, realized by reorientation of pigment molecules induced by trans-cis photoisomerization. We explore this photochemically switchable system using chromatographic analysis coupled with microimaging based on fluorescence lifetime and Raman scattering, showing it at work in both isolated human retina and model lipid membranes. The molecular mechanism underlying xanthophyll reorientation is explained in terms of hydrophobic mismatch using molecular dynamics simulations. Overall, we show that xanthophylls in the human retina act as "molecular blinds", opening and closing on a submillisecond timescale to dynamically control the intensity of light reaching the photoreceptors, thus enabling vision at a very low light intensity and protecting the retina from photodegradation when suddenly exposed to strong light.

Current treatment modalities in diabetic macular edema.

Diabetic macular edema is the major cause of vision impairment in the diabetic population. Its treatment requires a multidisciplinary approach and the use of both systemic and local therapies. Current management includes the vascular endothelial growth factor inhibitors and steroids administered as intravitreal injections, as well as laser therapy and surgical treatment. Treatment modalities in diabetic macular edema have changed in recent years, after the introduction of vascular endothelial growth factor inhibitors, which are gradually replacing laser photocoagulation. All anti-VEGF agents tested so far showed efficacy in the treatment of diabetic macular edema. Due to structural differences, the therapeutic efficacy of different anti-VEGF products varies. According to recent results, 2,0 mg of aflibercept is more effective than 0,3 mg of ranibizumab in patients with lower visual acuity at baseline. Additionally, its superiority was shown in reducing the number of required macular laser photocoagulation procedures. This article provides a comprehensive overview of available therapeutic modalities based on laser photocoagulation, anti-VEGF agents, steroid injections or surgical interventions, and discusses their efficacy in patients with diabetic macular edema.

Confocal Laser Scanning Tomography to Predict Visual Field Conversion in Patients With Ocular Hypertension and Early Glaucoma.

PURPOSE: To compare Moorfields regression analysis (MRA), Glaucoma probability score (GPS), and different discriminant functions to predict future visual field conversion of patients with ocular hypertension and early glaucoma. PATIENTS AND METHODS: The study included 120 eyes of patients with ocular hypertension and 110 eyes of patients with early glaucoma from the Erlangen glaucoma registry. Annually, all patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and HRT (Heidelberg Retina Tomograph I-III; Heidelberg Engineering) measurements. The cohort was divided into 2 groups based on the development of repeatable glaucomatous visual fields. Positive predictive values and negative predictive values were compared for MRA, GPS, and the classification of Bathija, Iester, Mardin, and Mikelberg at baseline. Kaplan-Meier Survival curves and Logrank tests were used to evaluate equality of survival distributions for different test results. RESULTS: Median follow-up was 9.04 years. 26 eyes (11.3%) demonstrated glaucomatous visual field loss in the follow-up. MRA temporal-superior and temporal-inferior outside normal limits were predictive of future visual field loss with positive predictive values of 33.3% and 28.6%. Normal GPS Temporal Sector demonstrated a negative predictive value of 96.4% and normal results in discriminant functions between 94.7% and 95.5%. CONCLUSIONS: Confocal scanning laser tomography is a useful imaging modality to predict future visual field conversion. Development of visual field defects in 10 years is highly unlikely, if GPS classification and/or classification of discriminant analysis at baseline are normal. MRA temporal-superior and temporal-inferior outside normal limits are associated with future VF conversion (ClinicalTrials.gov number, NCT00494923).

The Effect of Long-term Antiglaucomatous Drug Administration on Central Corneal Thickness.

PURPOSE: To evaluate rates of changes per year of central corneal thickness after antiglaucomatous drug administration with ß-blockers, prostaglandin analogs, and carbonic anhydrase inhibitors monotherapy and combined topical antiglaucomatous therapy, in a cohort of patients with ocular hypertension, glaucoma suspects, and patients with perimetric glaucoma as compared with normal controls. PATIENTS AND METHODS: This retrospective single-center study included 130 eyes as healthy controls, 121 eyes of ocular hypertensive patients, 105 eyes of glaucoma suspects, and 49 eyes of perimetric glaucoma patients. All patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and optical coherence pachymetry (OCP; Heidelberg Engineering). The cohort was divided into 8 groups on the basis of topical antiglaucomatous medication. Linear regression analysis was conducted to analyze the relationship between central corneal thickness and exposure to antiglaucomatous medication during the follow-up. RESULTS: Central corneal thickness did not change during the follow-up for investigated diagnostic subgroups. There was a statistically significant decrease in central corneal thickness for eyes treated with prostaglandin monotherapy (-3.1 µm/y for left eye), and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and ß-blockers (-5.8 and -3.8 µm/y for right and left eye, respectively). CONCLUSIONS: We recommend regular measurements before and during therapy with prostaglandin monotherapy and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and ß-blockers. Follow-up intraocular pressure measurements may be underestimated for eyes treated with the aforementioned treatment regimens if central corneal thickness is not measured on a regular basis.

Solitary sarcoid granuloma of the iris mimicking tuberculosis: a case report.

Introduction. We report a case of a male patient presented with sarcoid lesions of the iris and conjunctiva, mimicking tuberculosis due to epithelioid cell granulomas with small central necrosis in conjunctival biopsy. Patient. A 25-year-old man was referred to our department for further management of an "iris tumor with iridocyclitis" in his right eye. Initial examination showed an isolated vascular tumor of the iris and ciliary body with anterior uveitis and mutton-fat keratic precipitates, suggesting the diagnosis of a granulomatous disease. Conjunctival biopsy revealed granulomatous epithelioid cell inflammation with small central necrosis without acid-fast bacilli. Extensive systemic examination, including bronchoscopy and transbronchial biopsy, provided the diagnosis of sarcoidosis stage 2 with pulmonary involvement, thus ruling out tuberculosis. Systemic and local steroid therapy was initiated, leading to complete recovery of our patient with complete disappearance of the iris lesion and improvement of the pulmonary function. Conclusion. Although noncaseating epithelioid cell granulomas are typical for sarcoidosis, small central necrosis can be found in some granulomas, leading to presumption of tuberculosis. Extensive systemic checkup in cooperation with other specialists is essential to confirm the correct diagnosis and to initiate the appropriate therapy.

Glaucoma diagnostic performance of GDxVCC and spectralis OCT on eyes with atypical retardation pattern.

PURPOSE: To investigate the impact of typical scan score (TSS) on discriminating glaucomatous and healthy eyes by scanning laser polarimetry and spectral domain optical coherence tomography (SD-OCT) in 32 peripapillary sectors. PATIENTS AND METHODS: One hundred two glaucoma patients and 32 healthy controls underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, GDxVCC, and SD-OCT measurements. For controls, only very typical scans (TSS=100) were accepted. Glaucoma patients were divided into 3 subgroups (very typical: TSS=100; typical: 99≥TSS≥80, atypical: TSS<80). Receiver operating characteristic curves were constructed for mean retinal nerve fiber layer values, sector data, and nerve fiber indicator (NFI). Sensitivity was estimated at ≥90% specificity to compare the discriminating ability of each imaging modality. RESULTS: For discrimination between healthy and glaucomatous eyes with very typical scans, the NFI and inferior sector analyses 26 to 27 demonstrated the highest sensitivity at ≥90% specificity in GDxVCC and SD-OCT, respectively. For the typical and atypical groups, sensitivity at ≥90% specificity decreased for all 32 peripapillary sectors on an average by 10.9% and 17.9% for GDxVCC and by 4.9% and 0.8% for SD-OCT. For GDxVCC, diagnostic performance of peripapillary sectors decreased with lower TSS, especially in temporosuperior and inferotemporal sectors (sensitivity at ≥90% specificity decreased by 55.3% and by 37.8% in the atypical group). CONCLUSIONS: Diagnostic accuracy is comparable for SD-OCT and GDxVCC if typical scans (TSS=100) are investigated. Decreasing TSS is associated with a decrease in diagnostic accuracy for discriminating healthy and glaucomatous eyes by scanning laser polarimetry. NFI is less influenced than the global or sector retinal nerve fiber layer thickness. The TSS score should be included in the standard printout. Diagnostic accuracy of SD-OCT is barely influenced by low TSS.

Plasma homocysteine levels in patients with normal tension glaucoma.

PURPOSE: To investigate whether there is an association of elevated plasma levels of homocysteine (Hcy) and normal tension glaucoma (NTG). PATIENTS AND METHODS: Plasma levels of Hcy (fluorescence polarization immunoassay), vitamin B6 (high-performance liquid chromatography), vitamin B12, and folate levels (immunoassay) were determined in 42 patients with NTG and in 42 age-matched and sex-matched controls. RESULTS: No significant difference regarding Hcy (NTG: 10.95 µmol/L±2.65; controls: 11.29 µmol/L±2.76) (P=0.639), vitamin B6 (NTG: 14.45 ng/mL±12.89; controls: 13.57 ng/mL±10.41) (P=0.629), vitamin B12 (NTG: 387.73 pg/mL±282.04; controls: 423.27 pg/mL±188.85) (P=0.052) and folate (NTG: 9.45ng/mL±3.42; controls: 10.82 ng/mL±4.48) (P=0.181) levels were found between both groups. CONCLUSIONS: An association of elevated Hcy levels and NTG was not found and therefore a role of Hcy as a modifiable risk factor in the pathogenesis of NTG seems unlikely.

Comparison of scanning laser polarimetry and optical coherence tomography in quantitative retinal nerve fiber assessment.

PURPOSE: To investigate the relationship between retinal nerve fiber layer (RNFL) measurements in corresponding areas obtained with scanning laser polarimetry and optical coherence tomography and to compare their discriminating ability in the diagnosis of preperimetric and perimetric glaucoma. PATIENTS AND METHODS: Three hundred eighty-six subjects-57 healthy controls, 145 ocular hypertensive patients, 89 with preperimetric glaucoma, and 95 with perimetric glaucoma-were recruited from the Erlangen Glaucoma Registry. Perimetry, 24-hours intraocular pressure profile, stereographic optic disc slides, optical coherence tomography StratusOCT, and scanning laser polarimetry GDx VCC (Carl Zeiss Meditec, Inc, Dublin, CA) were performed in all patients. Receiver operating characteristic (ROC) curves were constructed for mean RNFL values, sector data, and indices. Sensitivity was estimated at >or=90% and >or=80% of specificity to compare the discriminating ability of each imaging modality. RESULTS: For discrimination between glaucomatous and healthy eyes in GDx VCC the nerve fiber index demonstrated the largest area under the ROC curve (AUROC) (0.962+/-0.013), whereas in StratusOCT the largest AUROC (0.986+/-0.006) was found in the inferior quadrant. For preperimetric glaucoma detection the nerve fiber index achieved the largest AUROC (0.783+/-0.037). In contrast, the total RNFL average obtained using StratusOCT showed the largest AUROC (0.904+/-0.025). Bland-Altman plots showed good agreement between both instruments. CONCLUSIONS: Both the GDx VCC and StratusOCT demonstrate increasing RNFL loss with advanced glaucomatous damage and were comparable in the diagnosis of perimetric glaucoma. Preperimetric glaucomatous damage may be better assessed by StratusOCT.

Influence of glaucomatous damage and optic disc size on glaucoma detection by scanning laser tomography.

PURPOSE: To investigate the impact of glaucomatous damage and optic disc size on different automated Heidelberg Retina Tomograph classifications for discriminating glaucoma and healthy controls. PATIENTS AND METHODS: Two hundred seventy-three glaucoma patients and 276 healthy controls were recruited from the Erlangen Glaucoma Registry. Standard static white on white perimetry, 24-hour intraocular pressure profile, stereographic optic disc slides, and scanning laser tomography were performed in all patients and controls. The effect of glaucoma stage and disc size on the diagnostic accuracy was evaluated using receiver operating characteristic curves. Results of the Glaucoma Probability Score were compared with other recently described multivariate classifications. RESULTS: Areas under the receiver operating characteristic curves for discrimination between glaucoma and healthy eyes of the overall classification by Glaucoma Probability Score, Moorfields regression analysis, Bathija, Iester, Mikelberg, and Mardin increased from 0.71, 0.65, 0.70, 0.67, 0.65, and 0.63 for early glaucoma (Jonas: stage I) to 0.96, 0.95, 0.94, 0.94, 0.92, and 0.88 for advanced glaucomatous damage (Jonas: stage IV). Best performance of discrimination between glaucoma and healthy eyes using area under the receiver operating characteristic curve's were observed for medium-sized discs (2.1 to 2.49 mm) and worst performance for large optic discs (>3.1 mm). Glaucoma Probability Score classification was superior to other investigated classifications in most of the investigated subgroups. CONCLUSIONS: The diagnostic accuracy of all classifications depends on the optic disc size and the glaucoma stage. Glaucoma Probability Score showed a better diagnostic performance than Moorfields regression analysis and was similar to that of Bathija.

Visualization of changes of the iris configuration after peripheral laser iridotomy in primary melanin dispersion syndrome using optical coherence tomography.

Pigment or melanin dispersion syndrome is characterized by radial iris transillumination defects, retrocorneal Krukenberg spindle, and dense trabecular pigmentation. Reverse pupillary block has been presumed as one possible pathogenetic mechanism for backward bowing of the iris leading to iris-zonular rubbing and distribution of melanin granules in the anterior chamber. Laser iridotomy is recommended as a treatment to prevent further melanin dispersion and development of pigmentary glaucoma. The effect of Nd:YAG laser iridotomy as a prophylactic and potentially causal treatment in melanin dispersion syndrome can be easily visualized by optical coherence tomography as a fast and noncontact procedure.

Measuring contrast sensitivity in normal subjects with OPTEC 6500: influence of age and glare.

BACKGROUND: The purpose of this study was to develop age-related curves for contrast sensitivity (CS) in normal subjects under day and night conditions with and without glare. METHODS: Sixty-one healthy eyes from 61 subjects were measured with the OPTEC(R) 6500 P under day and night conditions (luminance levels: 85 cd/m(2) and 3.0 cd/m(2) with and without glare; spatial frequencies: 1.5, 3, 6, 12 and 18 cycles/degree). A reliability analysis with five repeated measurements of six persons on 4 days was performed to examine the repeatability. The influence of age on contrast sensitivity, forward and backward scatter was examined by means of linear regression. RESULTS: Contrast sensitivity was significantly reduced under night conditions with glare, whereas glare had less influence under daylight illumination. Mean reliability coefficients are 0.87 (day), 0.77 (day with glare), 0.69 (night) and 0.81 (night with glare), which suggests sufficient retest reliability of the device. Regression analyses showed a highly significant influence of age, but the variance of the measurement values is not explained by age alone. The coefficients of determination for the regression of area under the log contrast sensitivity function (AULCSF) on age are 0.33 (photopic), 0.34 (photopic with glare), 0.29 (mesopic) and 0.36 (mesopic with glare, p < 0.0001 in all cases). CONCLUSION: A significant relationship between age, CS and scatter was confirmed in our study. The results provide baseline values for the examination of patients with different diseases in which contrast sensitivity is impaired (such as glaucoma, cataracts and amblyopia) and might be useful in studies of roadworthiness or in investigation of the impact of intraocular lenses.

Content of kynurenic acid and activity of kynurenine aminotransferases in mammalian eyes.

The present study investigated the kynurenic acid (KYNA) contents and kynurenine aminotransferase (KAT I and II) activity in structures of the human, monkey, rabbit and bovine eye. KYNA levels were investigated with HPLC and detected fluorimetrically. The activity of KAT I and II was assayed as quantitative analysis of newly synthesized KYNA in vitro. Mean KYNA levels (+/-SD) in the human retina and vitreous body were 36.8 +/- 7.6 and 33.1 +/- 6.2 pmol/g wet tissue weight, respectively. In human eyes, KAT I activity in the vitreous body was 0.57 +/- 0.28, that of KAT II was 2.56 +/- 0.69. KAT I activity in the retina was 3.42 +/- 1.17 and that of KAT II 10.75 +/- 9.2. (KAT activity is expressed as KYNA synthesis in picomoles per gram wet tissue weight per hour.) The values of KYNA and KAT observed in other mammalian species tested were in the same range. In conclusion, KYNA and KAT enzymatic activity are present in the structures of human and other mammalian eyes.