Visible Blue Light Therapy: Molecular Mechanisms and Therapeutic Opportunities.

BACKGROUND: Visible light is absorbed by photoacceptors in pigmented and non-pigmented mammalian cells, activating signaling cascades and downstream mechanisms that lead to the modulation of cellular processes. Most studies have investigated the molecular mechanisms and therapeutic applications of UV and the red to near infrared regions of the visible spectrum. Considerably less effort has been dedicated to the blue, UV-free part of the spectrum. OBJECTIVE: In this review, we discuss the current advances in the understanding of the molecular photoacceptors, signaling mechanisms, and corresponding therapeutic opportunities of blue light photoreception in non-visual mammalian cells in the context of inflammatory skin conditions. METHODS: The literature was scanned for peer-reviewed articles focusing on the molecular mechanisms, cellular effects, and therapeutic applications of blue light. RESULTS: At a molecular level, blue light is absorbed by flavins, porphyrins, nitrosated proteins, and opsins; inducing the generation of ROS, nitric oxide release, and the activation of G protein coupled signaling. Limited and contrasting results have been reported on the cellular effects of blue light induced signaling. Some investigations describe a regulation of proliferation and differentiation or a modulation of inflammatory parameters; others show growth inhibition and apoptosis. Regardless of the elusive underlying mechanism, clinical studies show that blue light is beneficial in the treatment of inflammatory skin conditions. CONCLUSION: To strengthen the use of blue light for therapeutic purposes, further in depth studies are clearly needed with regard to its underlying molecular and cellular mechanisms, and their translation into clinical applications.

Baseline mean deviation and rates of visual field change in treated glaucoma patients.

PURPOSE: To evaluate the relationships between baseline visual field (VF) mean deviation (MD) and subsequent progression in treated glaucoma. METHODS: Records of patients seen in a glaucoma practice between 1999 and 2009 were reviewed. Patients with glaucomatous optic neuropathy, baseline VF damage, and ≥8 SITA-standard 24-2 VF were included. Patients were divided into tertiles based upon baseline MD. Automated pointwise linear regression determined global and localized rates (decibels (dB) per year) of change. Progression was defined when two or more adjacent test locations in the same hemifield showed a sensitivity decline at a rate of >1.0 dB per year, P<0.01. RESULTS: For mild, moderate, and severe groups, progression was noted in 29.5, 31.2, and 26.0% of eyes (P=0.50) and global rates of VF change of progressing eyes were -1.3±1.2, -1.01±0.7, and -0.9±0.5 dB/year (P=0.09, analysis of variance). Within these groups, intraocular pressure (IOP) in stable vs progressing eyes were 15.5±3.3 vs 17.0±3.1 (P<0.01), 15.4±3.3 vs 15.9±2.5 (P=0.28), and 14.0±2.8 vs 14.8±2.3 mm Hg (P=0.07). More glaucoma filtering surgeries were performed in eyes with worse MD. There was no significant difference between groups regarding their risk of progression in both univariate (P=0.50) and multivariate (P=0.26) analyses adjusting for differences in follow-up IOP. CONCLUSIONS: After correcting for differences in IOP in treated glaucoma patients, we did not find a relationship between the rate of VF change (dB per year) and the severity of the baseline VF MD. This finding may have been due to more aggressive IOP lowering in eyes with more severe disease. Eyes with lower IOP progressed less frequently across the spectrum of VF loss.

Comparisons of anterior segment biometry between Chinese and Caucasians using anterior segment optical coherence tomography.

PURPOSE: To compare anterior segment parameters between eyes of Chinese and Caucasians using anterior segment optical coherence tomography and to evaluate the association between these parameters and anterior chamber angle width between the two ethnic groups. METHODS: 60 Chinese and 60 Caucasians, 30 with open angles and 30 with narrow angles (defined as Shaffer grade < or =2 in > or =3 quadrants during dark room gonioscopy) in each group, were consecutively enrolled. One eye of each subject was randomly selected for imaging in a completely darkened room. Measurements, including anterior chamber depth (ACD), scleral spur-to-scleral spur distance (anterior chamber width (ACW)), anterior chamber angle width, iris convexity and iris thickness, were compared between the groups. The associations between angle opening distance and biometric measurements were evaluated with univariate and multivariate regression analyses. RESULTS: There were no differences in age, axial length, anterior chamber angle measurements, pupil diameter and iris convexity between Chinese and Caucasians in both open-angle and narrow-angle groups. However, the ACD and ACW were smaller and the iris was thicker in Chinese. In the multivariate analysis, the ACD was the most influential biometric parameter for angle opening distance in both Chinese and Caucasians. After adjusting the effects of axial length, age and sex, ACD and ACW were significantly smaller in Chinese. CONCLUSIONS: Chinese eyes had smaller ACD, smaller ACW and greater iris thickness than Caucasians. ACD was the most influential parameter in determining the angle width in both ethnic groups.

Retinal vascular occlusions occur more frequently in the more affected eye in exfoliation syndrome.

PURPOSE: To evaluate the relationship between retinal vascular occlusions (RVOs) and exfoliation syndrome (XFS) in a cohort of patients with the two conditions. METHODS: We reviewed the records of patients with XFS with or without glaucoma and any type of RVO between 1983 and 2007. Patients with prior incisional surgery or a history of uveitis were excluded. Data collected included demographics, systemic comorbidities, type of RVO, and intraocular pressure (IOP) before the RVO. Slit-lamp biomicroscopy regarding the presence of exfoliation material on the lens capsule and pupillary margin before the vascular event was used to evaluate the laterality and degree of XFS. RESULTS: We identified 36 patients (mean age 78.4+/-8.3 years, 19 women). Most patients were of European descent (34/36) and 20 (56%) had no prior glaucoma diagnosis. The most common retinal vascular events were central retinal vein occlusion (18/36) and BRVO (10/36). Mean IOP between eyes with (19.5+/-6.5 mm Hg) and without (17.9+/-4.8 mm Hg) RVO was similar (P=0.12). RVOs occurred more commonly in the eye with more pronounced XFS in 92% (33/36) of the cases. A similar agreement was found when considering patients with and without glaucoma separately (94% (15/16) vs90% (18/20); P=0.83). In addition, no difference in the agreement percentage was observed when comparing patients with unilateral XFS (87% (13/15)) with all study patients (P=0.87). CONCLUSIONS: Retinal vascular occlusion in patients with XFS occurs most often in the affected or more severely affected eye. As vascular occlusions happened in patients with and without glaucoma in similar proportions, the presence of XFS seems to play an important role in these findings.

A comparison between microperimetry and standard achromatic perimetry of the central visual field in eyes with glaucomatous paracentral visual-field defects.

BACKGROUND AND AIMS: The aim was to correlate retinal sensitivity as determined by scanning laser ophthalmoscope microperimetry (SLO-MP) in glaucomatous eyes with paracentral visual field (VF) defects detected by standard automated perimetry (SAP). METHODS: Twenty eyes with glaucomatous optic neuropathy and an SAP VF defect involving the central 16 test points (at least one point with p<1% in the 24-2 VF) were enrolled. Eyes with diseases other than glaucoma were excluded. All patients underwent SLO-MP and SAP of the central 10 degrees . Results from each eye were divided into four quadrants for analysis. Normal and abnormal quadrants by SAP were compared with the corresponding normal and abnormal quadrants by SLO-MP. Regression analysis was used to correlate the mean threshold values (dB) of SLO-MP and SAP in each quadrant. Macular optical coherence tomography (OCT) was performed when there was a disagreement between functional tests. RESULTS: The mean age and VF mean deviation were 60.8 (13.4) years and -7.3 (6.1) dB, respectively. There was a significant correlation between SLO-MP and SAP results in all quadrants (r(2)> or =0.68, p<0.001). All abnormal SAP quadrants had a corresponding abnormal SLO-MP quadrant. However, 21% of the normal SAP quadrants had an abnormal corresponding microperimetry result; a corresponding significant reduction in total macular thickness measured by OCT was present in 75% of these quadrants. CONCLUSIONS: Macular sensitivity evaluated by SLO-MP correlates significantly with SAP paracentral VF defects. SLO-MP detected retinal sensitivity reduction in areas of OCT structural damage with normal SAP and suggests that subtle paracentral functional deficits may be present in many more eyes with established glaucoma than generally assumed.

Posterior chamber volume does not change significantly during dilation.

BACKGROUND/AIMS: To determine whether the volume of the posterior chamber changes during pupillary dilation. METHODS: Eyes with anatomically narrow angles underwent ultrasound biomicroscopy of the posterior chamber and pupillary margin under dark- and light-room conditions to assess changes in posterior chamber anatomy and volume. All examinations were stored as real-time video. A frame-by-frame analysis was performed using a macro written for the ImageJ image-processing software. RESULTS: Thirteen eyes were assessed. The mean patient age was 63.0 (SD 10.0) years, and the mean refractive error was 1.1 (1.9) dioptres. The horizontal mean pupillary diameter was 2.3 (0.6) mm and 3.5 (0.5) mm under light- and dark-room conditions, respectively (p<10(-7), paired t test). The mean posterior chamber volumes were unchanged under light and dark conditions (3.76 (1.09) vs 3.63 (0.78) mm(3), p = 0.22, paired t test). Volumes were greater under light conditions in eight eyes and under dark conditions in five eyes. CONCLUSIONS: The volume of the posterior chamber does not change significantly during dilation.

Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage.

AIM: To assess the accuracy of optical coherence tomography (OCT) in detecting damage to a hemifield, patients with hemifield defects confirmed on both static automated perimetry (SAP) and multifocal visual evoked potentials (mfVEP) were studied. METHODS: Eyes of 40 patients with concomitant SAP and mfVEP glaucomatous loss and 25 controls underwent OCT retinal nerve fibre layer (RNFL), mfVEP and 24-2 SAP tests. For the mfVEP and 24-2 SAP, a hemifield was defined as abnormal based upon cluster criteria. On OCT, a hemifield was considered abnormal if one of the five clock hour sectors (3 and 9 o'clock excluded) was at <1% (red) or two were at <5% (yellow). RESULTS: Seventy seven (43%) of the hemifields were abnormal on both mfVEP and SAP tests. The OCT was abnormal for 73 (95%) of these. Only 1 (1%) of the 100 hemifields of the controls was abnormal on OCT. Sensitivity/specificity (one eye per person) was 95/98%. CONCLUSIONS: The OCT RNFL test accurately detects abnormal hemifields confirmed on both subjective and objective functional tests. Identifying abnormal hemifields with a criterion of 1 red (1%) or 2 yellow (5%) clock hours may prove useful in clinical practice.

Urrets-Zavalia syndrome as a complication of argon laser peripheral iridoplasty.

OBJECTIVE: To report on 8 patients who developed prolonged mydriasis after argon laser peripheral iridoplasty (ALPI). DESIGN: Retrospective case series. METHODS: A review of the charts of 8 patients with persistent occludable angles after laser iridotomy who developed mydriasis after undergoing ALPI. RESULTS: 12 eyes of 8 patients (mean age 50.2, standard deviation 6.9, range 40-61 years) developed persistent dilatation. 7 of 8 patients had plateau iris syndrome. Only one patient had a decrease in visual acuity. Intraocular pressure increased only in 1 eye and remained stable or decreased in the others. Of the 8 patients, 7 had blurred vision, 2 had photophobia, 4 had glare and 1 had discomfort. The pupillary response to pilocarpine instillation was minimal or absent. Mydriasis eventually resolved in all eyes without treatment. CONCLUSION: ALPI can be complicated by mydriasis unresponsive to pilocarpine. Mydriasis and accompanying symptoms resolved spontaneously within 1 year in most patients.

Axial length and optic disc size in normal eyes.

AIM: To investigate the relationship between optic disc area and axial length in normal eyes of white and black people. METHODS: Consecutive eligible normal subjects were enrolled. Ocular biometry was obtained using A-scan ultrasonography, and reliable images of the optic disc were obtained using a confocal scanning laser ophthalmoscope. The relationship between optic disc area and axial length was assessed using univariate and multivariate models. RESULTS: 281 eyes of 281 subjects were enrolled. Black subjects (n = 157) had significantly larger discs (mean (SD) disc area, 2.12 (0.5) mm(2)) than white subjects (n = 124; 1.97 (0.6) mm(2); t test, p = 0.02). Optic disc area increased with axial length (Pearson's correlation coefficient, r = 0.13, p<0.035) for the entire study population. Multivariate regression models including race, disc area and axial length showed that a significant but weak linear relationship exists between axial length and disc area (partial correlation coefficient 0.14; p<0.024), and with race and disc area (partial correlation coefficient 0.19; p<0.017) when adjusted for the effects of other terms in the model. CONCLUSION: Increased disc area is associated with longer axial length measurements and African ancestry. This may have implications for pathophysiology and risk assessment of glaucoma.

Structural and functional assessment of the macular region in patients with glaucoma.

PURPOSE: To investigate the correlation of a structural measure of the macular area (optical coherence tomography (OCT)) with two functional measures (10-2 Humphrey visual field (HVF) and multifocal visual evoked potential (mfVEP)) of macular function. METHODS: 55 eyes with open-angle glaucoma were enrolled. The 10-2 HVF was defined as abnormal if clusters of > or =3 points with p<5%, one of which had p<1%, were present. The mfVEP was abnormal if probability plots had > or =2 adjacent points with p<1%, or > or =3 adjacent points with p<5% and at least one of these points with p<1%. Two criteria were used for the macular OCT: (I) > or =2 sectors with p<5% or 1 sector with p<1% and (II) 1 sector with p<5%. RESULTS: 54 of the 55 eyes showed an abnormal 10-2 HVF and 50 had central mfVEP defects. The two OCT criteria resulted in sensitivities of 85% and 91%. When both functional tests showed a defect (in 49 eyes), the OCT was abnormal in 45. For the OCT the outer and inner inferior regions were the most likely to be abnormal, and both functional techniques were most abnormal in the superior hemifield. CONCLUSIONS: Good agreement exists between macular thickness and functional defects in patients with glaucoma. Study of the macular region may provide a quantitative measure for disease staging and monitoring.

Detection of glaucoma using operator-dependent versus operator-independent classification in the Heidelberg retinal tomograph-III.

OBJECTIVE: To compare the abilities of a new Glaucoma Probability Scoring (GPS) system and Moorfields regression analysis (MRA) to differentiate between glaucomatous and normal eyes using Heidelberg retinal tomograph (HRT)-III software and race-specific databases. METHODS: In this prospective study, one eye (refractive error < or =5 D) each of consecutive normal patients and those with glaucoma was enrolled. All patients underwent a full eye examination, standard achromatic perimetry (Swedish Interactive Threshold Algorithm-standard automated perimetry (SITA-SAP), program 24-2) and confocal scanning laser ophthalmoscopy (HRT-II) within 1 month. Normal patients had two normal visual fields in both eyes (pattern standard deviation (PSD) >5% and Glaucoma Hemifield Test within 97% normal limits) and a normal clinical examination. Glaucoma was defined on the basis of SITA-SAP visual field loss (PSD<5% or Glaucoma Hemifield Test outside normal limits) on two consecutive visual fields. HRT-II examinations were exported to the HRT-III software (V.3.0), which uses an enlarged race-specific database, consisting of 733 eyes of white people and 215 eyes of black people. Race-adjusted MRA for the most abnormal sector (operator-dependent contour line placement) was compared with the global race-adjusted GPS (operator independent). MRA sectors outside the 99.9% confidence interval limits (outside normal limits) and GPS > or =0.64 were considered abnormal. RESULTS: 136 normal patients (72 black and 64 white patients) and 84 patients with glaucoma (52 black and 32 white patients) were enrolled (mean age 50.4 (SD 14.4) years). The average visual field mean deviation was (-)0.4 (SD 1.1) db for the normal group and (-)7.3 (SD 6.7) db for the glaucoma group (p<0.001). Mean GPS values were 0.21 (SD 0.23) and 0.73 (SD 0.27) for normal and glaucomatous eyes, respectively (p<0.001). Sensitivity and specificity values were 77.1% and 90.3% for GPS, and 71.4% and 91.9% for MRA, respectively. CONCLUSIONS: In this cohort, GPS software sensitivity and specificity values are similar to those of MRA, which requires placement of an operator-dependent contour line. The development of software to detect glaucoma without a contour line is critical to improving the potential use of HRT as a tool for glaucoma detection and screening.

The effects of glaucoma on the latency of the multifocal visual evoked potential.

AIMS: To determine the effect of glaucomatous damage on the latency of the multifocal visual evoked potential (mfVEP). METHODS: Monocular mfVEPs were recorded from a glaucoma group (n = 50) defined by a glaucomatous disc and an abnormal visual field and a control group (n = 47). 25 patients were characterised as normal tension glaucoma (NTG) and 25 as high tension glaucoma (HTG). Monocular and interocular latency analyses of the more affected eye were obtained using custom software. RESULTS: On interocular analysis, both the HTG and NTG groups showed a statistically significant increase in mean mfVEP latency with average relative latencies and percentage of points with significant delays of 1.7 ms and 10.3% (HTG) and 1.3 ms and 8.2% (NTG) compared to -0.3 ms and 2.7% (controls). On monocular analysis, only the HTG group showed a significant increase in latency with measures of 5.7 ms and 14.6% (HTG) compared to 3.2 ms and 10.6% (NTG) and 2.1 ms and 9.6% (controls). Using the 95th percentile of a normative group as the cut off, the sensitivity ranged from 20% to 38% and the specificity from 87% to 100% with the interocular analysis providing the best discrimination, CONCLUSION: Although up to 40% of patients showed delays in the mfVEP latency, these delays were modest, on average a few milliseconds. These results differ markedly from those of a recent conventional VEP study, which reported 100% sensitivity, 100% specificity, and an average delay that exceeded 25 ms.