High correlated color temperature artificial lighting impairs retinal pigment epithelium integrity and chloride ion transport: A potential mechanism for choroidal thinning.

Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.

Influence of Aberration-Free, Narrowband Light on the Choroidal Thickness and Eye Length.

Purpose: To determine whether light chromaticity without defocus induced by longitudinal chromatic aberration (LCA) is sufficient to regulate eye growth. Methods: An interferometric setup based on a spatial light modulator was used to illuminate the dominant eyes of 23 participants for 30 minutes with three aberration-free stimulation conditions: (1) short wavelength (450 nm), (2) long wavelength (638 nm), and (3) broadband light (450-700 nm), covering a retinal area of 12°. The non-dominant eye was occluded and remained as the control eye. Axial length and choroidal thickness were measured before and after the illumination period. Results: Axial length increased significantly from baseline for short-wavelength (P < 0.01, 7.4 ± 2.2 µm) and long-wavelength (P = 0.01, 4.8 ± 1.7 µm) light. The broadband condition also showed an increase in axial length with no significance (P = 0.08, 5.1 ± 3.5 µm). The choroidal thickness significantly decreased in the case of long-wavelength light (P < 0.01, -5.7 ± 2.2 µm), but there was no significant change after short-wavelength and broadband illumination. The axial length and choroidal thickness did not differ significantly between the test and control eyes or between the illumination conditions (all P > 0.05). Also, the illuminated versus non-illuminated choroidal zone did not show a significant difference (all P > 0.05). Conclusions: All stimulation conditions with short- and long-wavelength light and broadband light led to axial elongation and choroidal thinning. Therefore, light chromaticity without defocus induced by LCA is suggested to be insufficient to regulate eye growth. Translational Relevance: This study helps in understanding if light chromaticity alone is a sufficient regulator of eye growth.

Short-Term Exposure to Blue Light Shows an Inhibitory Effect on Axial Elongation in Human Eyes Independent of Defocus.

Purpose: Given the potential role of light and its wavelength on ocular growth, we investigated the effect of short-term exposure to the red, green, and blue light on ocular biometry in the presence and absence of lens-induced defocus in humans. Methods: Twenty-five young adults were exposed to blue (460 nm), green (521 nm), red (623 nm), and white light conditions for 1-hour each on 4 separate experimental sessions conducted on 4 different days. In each light condition, hyperopic defocus (3D) was induced to the right eye with the fellow eye experiencing no defocus. Axial length and choroidal thickness were measured before and immediately after the light exposure with a non-contact biometer. Results: Axial length increased from baseline after red light (mean difference ± standard error in the defocussed eye and non-defocussed eye = 11.2 ± 2 µm and 6.4 ± 2.3 µm, P < 0.001 and P < 0.01, respectively) and green light exposure (9.2 ± 3 µm and 7.0 ± 2.5 µm, P < 0.001 and P < 0.001) with a significant decrease in choroidal thickness (P < 0.05, both red and green light) after 1-hour of exposure. Blue light exposure resulted in a reduction in axial length in both the eyes (-8.0 ± 3 µm, P < 0.001 in the defocussed eye and -6.0 ± 3 µm, P = 0.11 in the non-defocused eye) with no significant changes in the choroidal thickness. Conclusions: Exposure to red and green light resulted in axial elongation, and blue light resulted in inhibition of axial elongation in human eyes. Impact of such specific wavelength exposure on children and its application in myopia control need to be explored.

Risk factors associated with progression of diabetic retinopathy in eyes treated with panretinal photocoagulation.

Uncontrolled diabetes has been associated with progression of diabetic retinopathy (DR) in several studies. Therefore, we aimed to investigate systemic and ophthalmic factors related to worsening of DR even after completion of panretinal photocoagulation (PRP). We retrospectively reviewed DR patients who had completed PRP in at least one eye with a 3-year follow-up. A total of 243 eyes of 243 subjects (mean age 52.6 ± 11.6 years) were enrolled. Among them, 52 patients (21.4%) showed progression of DR after PRP (progression group), and the other 191 (78.6%) patients had stable DR (non-progression group). The progression group had higher proportion of proliferative DR (P = 0.019); lower baseline visual acuity (P < 0.001); and higher platelet count (P = 0.048), hemoglobin (P = 0.044), and hematocrit, (P = 0.042) than the non-progression group. In the multivariate logistic regression analysis for progression of DR, baseline visual acuity (HR: 0.053, P < 0.001) and platelet count (HR: 1.215, P = 0.031) were identified as risk factors for progression. Consequently, we propose that patients with low visual acuity or high platelet count are more likely to have progressive DR despite PRP and require careful observation. Also, the evaluation of hemorheological factors including platelet counts before PRP can be considered useful in predicting the prognosis of DR.

A nonhuman primate model of blue light-induced progressive outer retina degeneration showing brimonidine drug delivery system-mediated cyto- and neuroprotection.

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) characterized by atrophy of the retinal pigment epithelium (RPE), loss of photoreceptors, and disruption of choriocapillaris. Excessive light exposure is toxic to the retina and is a known risk factor for AMD. We first investigated the effects of blue light-induced phototoxicity on RPE and photoreceptors in nonhuman primates (NHPs, a model of progressive retinal degeneration) and then evaluated the potential cyto- and neuroprotective effects of the brimonidine drug delivery system (Brimo DDS). In the first set of experiments related to model development, parafoveal lesions of varying severity were induced using blue light irradiation of the retina of cynomolgus monkeys to evaluate the level of phototoxicity in the RPE and photoreceptors. RPE damage was assessed using fundus autofluorescence imaging to quantify areas of hypofluorescence, while thinning of the outer nuclear layer (ONL, photoreceptor nuclei) was quantified using optical coherence tomography (OCT). Photoreceptor function was assessed using multifocal electroretinography (mfERG). RPE damage progressively increased across all lesion severities from 2 to 12 weeks, as did the extent of ONL thinning. Lesions of high severity continued to show reduction in mfERG amplitude, reaching a statistically significant maximum reduction at 12 weeks. Collectively, the first set of experiments showed that blue light irradiation of the NHP eye resulted in progressive retinal degeneration identified by damage to RPE, ONL thinning, and disrupted photoreceptor function - hallmarks of GA in humans. We then used the model to evaluate the cyto- and neuroprotective effects of Brimo DDS, administered as a therapeutic after allowing the lesions to develop for 5 weeks. Placebo DDS or Brimo DDS were administered intravitreally and a set of untreated animals were used as an additional control. In the placebo DDS group, hypofluorescence area continued to increase from baseline, indicating progressive RPE damage, while progression was significantly slowed in eyes receiving Brimo DDS. Likewise, ONL thinning continued to progress over time in eyes that received the placebo DDS, but was reduced in Brimo DDS-treated eyes. Pharmacologically relevant brimonidine concentrations were sustained in the retina for up to 26 weeks following Brimo DDS administration. In summary, Brimo DDS demonstrated cyto- and neuroprotective effects in a novel NHP GA model of progressive retinal degeneration.

Effects of Narrowband Light on Choroidal Thickness and the Pupil.

Purpose: To determine the effects of narrowband light exposure on choroidal thickness and the pupil response in humans. Methods: Twenty subjects, ages 21 to 43 years, underwent 1 hour of exposure to broadband, short wavelength "blue," or long wavelength "red" light, or darkness. Choroidal thickness, imaged with spectral domain optical coherence tomography, axial length, determined from biometry, and rod/cone- and intrinsically photosensitive retinal ganglion cell-driven pupil responses were measured before and after exposure. Pupil stimuli were six 1 second alternating red (651 nm) and blue (456 nm) stimuli, 60 seconds apart. Pupil metrics included maximum constriction and the 6 second post-illumination pupil response (PIPR). Results: Compared with before exposure, the choroid significantly thinned after broadband light, red light, and dark exposure (all P < 0.05), but not after blue light exposure (P = 0.39). The maximum constriction to 1 second red stimuli significantly decreased after all light exposures (all P < 0.001), but increased after dark exposure (P = 0.02), compared with before exposure. Maximum constriction and 6-second PIPR to 1 second blue stimuli significantly decreased after all light exposures compared with before exposure (all P < 0.005), with no change after dark exposure (P > 0.05). There were no differences in axial length change or 6-second PIPR to red stimuli between exposures. Conclusions: Narrowband blue and red light exposure induced differential changes in choroidal thickness. Maximum constriction, a function of rod/cone activity, and the intrinsically photosensitive retinal ganglion cell-mediated PIPR were attenuated after all light exposures. Findings demonstrate differing effects of short-term narrowband light and dark exposure on the choroid, rod/cone activity, and intrinsically photosensitive retinal ganglion cells.

EFFICACY OF DOUBLE DOSE PHOTODYNAMIC THERAPY FOR CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: To evaluate the efficacy of photodynamic therapy using a double dose of verteporfin for patients with circumscribed choroidal hemangioma. METHODS: This retrospective comparative case series evaluated data from 10 patients who were treated using double dose photodynamic therapy (12 mg/m) and seven patients who were treated using the standard dose (6 mg/m). A laser was applied with a radiant exposure of 50 J/cm. The ophthalmologic examinations were performed at baseline and 1 year after the treatment and included best-corrected visual acuity, slit-lamp biomicroscopy, fundus examination, spectral domain optical coherence tomography, and B-scan ultrasonography. RESULTS: The mean age in the double dose group was 51.60 years, compared with 50.57 years in the standard-dose group. The only significant difference between the two groups' baseline characteristics was observed in their initial tumor heights. Foveal center thickness, subretinal fluid, and subfoveal choroidal thickness decreased significantly at 1 year after treatment in both groups. Tumor height and the greatest linear dimension of the tumor's base only decreased significantly in the double dose group (P = 0.031). Both groups did not experience significant visual improvements. CONCLUSION: Double dose photodynamic therapy was effective and safe for treating circumscribed choroidal hemangioma and provided better tumor regression with similar resorption of subretinal fluid, compared with standard-dose photodynamic therapy.

Targeted Imaging of VCAM-1 mRNA in a Mouse Model of Laser-Induced Choroidal Neovascularization Using Antisense Hairpin-DNA-Functionalized Gold-Nanoparticles.

Mouse laser-induced choroidal neovascularization (mouse LCNV) recapitulates the "wet" form of human age-related macular degeneration (AMD). Vascular cell adhesion molecule-1 (VCAM-1) is a known inflammatory biomarker, and it increases in the choroidal neovascular tissues characteristic of this experimental model. We have designed and constructed gold nanoparticles (AuNPs) functionalized with hairpin-DNA that incorporates an antisense sequence complementary to VCAM-1 mRNA (AS-VCAM-1 hAuNPs) and tested them as optical imaging probes. The 3' end of the hairpin is coupled to a near-infrared fluorophore that is quenched by the AuNP surface via Förster resonance energy transfer (FRET). Hybridization of the antisense sequence to VCAM-1 mRNA displaces the fluorophore away from the AuNP surface, inducing fluorescent activity. In vitro testing showed that hAuNPs hybridize to an exogenous complementary oligonucleotide within a pH range of 4.5-7.4, and that they are stable at reduced pH. LCNV mice received tail-vein injections of AS-VCAM-1 hAuNPs. Hyperspectral imaging revealed the delivery of AS-VCAM-1 hAuNPs to excised choroidal tissues. Fluorescent images of CNV lesions were obtained, presumably in response to the hybridization of AS-hAuNPs to LCNV-induced VCAM-1 mRNA. This is the first demonstration of systemic delivery of hAuNPs to ocular tissues to facilitate mRNA imaging of any target.

Removal of choroidal vasculature using concurrently applied ultrasound bursts and nanosecond laser pulses.

Pathologic microvasculature plays a crucial role in innumerable diseases causing death and major organ impairment. A major clinical challenge is the development of selective therapies to remove these diseased microvessels without damaging surrounding tissue. This report describes our development of novel photo-mediated ultrasound therapy (PUT) technology for precisely removing choroidal blood vessels in the eye. PUT selectively removes microvessels by concurrently applying nanosecond laser pulses with ultrasound bursts. In PUT experiments on rabbit eyes in vivo, we applied 55-75 mJ/cm2 of light fluence at the retinochoroidal surface at 532-nm and 0.5 MPa of ultrasound pressure at 0.5 MHz. PUT resulted in significantly reduced blood perfusion in the choroidal layer which persisted to four weeks without causing collateral tissue damage, demonstrating that PUT is capable of removing choroidal microvasculature safely and effectively. With its unique advantages, PUT holds potential for the clinical management of eye diseases associated with microvessels and neovascularization.

Evaluation of Vascular Changes with Optical Coherence Tomography Angiography after Plaque Radiotherapy of Choroidal Melanoma.

AIM: The purpose of this paper was to evaluate whether optical coherence tomography angiography (OCT-A) can be used to quantify the vascular changes in radiation maculopathy, and changes in the tumor vasculature in eyes treated with plaque radiotherapy for choroidal melanoma. METHODS: In this prospective study, we evaluated 39 Caucasian patients with choroidal melanoma (39 eyes) treated with ruthenium-106 plaque radiotherapy. The patients underwent complete ophthalmic examination, bulbar echography, and OCT-A before and 1 year after treatment. RESULTS: At baseline, the mean best-corrected visual acuity (BCVA) in the affected eyes was 0.35 ± 0.40 logMAR, and the mean tumor thickness was 2.68 ± 0.25 mm at A-scan echography. After treatment, the mean BCVA increased to 0.41 logMAR, the mean tumor thickness decreased to 1.66 ± 0.23 mm, and the tumor basal diameter was significantly reduced (U = 108, p = 0.001). Moreover, the capillary vessel density was significantly lower in all Early Treatment of Diabetic Retinopathy Study sectors, and both the vessel and flow areas were significantly reduced (p = 0.030 and p = 0.001, respectively). CONCLUSIONS: OCT-A is a noninvasive, reliable method with which to quantify the vessel changes in radiation maculopathy and, given the association between vascularization and malignancy, this procedure may be an aid in treatment decision-making and in monitoring the efficacy of treatment.

Subfoveal Choroidal Thickness as a Potential Predictor of Clinical Response to Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Stereotactic radiotherapy (SRT) is a new adjuvant treatment modality that has been shown to reduce the need for repetitive intravitreal injections (IVIs) in patients with neovascular age-related macular degeneration (nAMD). The authors aimed to determine baseline predictors of clinical response to SRT. PATIENTS AND METHODS: This was a retrospective, observational case series of patients with nAMD who underwent SRT and subsequently had at least 12 months of complete follow-up. After SRT and one mandatory IVI, patients were examined every 4 weeks and received further treatment on a pro re nata basis. Examination included enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT) to measure subfoveal choroidal thickness (SFCT) and central macular thickness (CMT). Patients' data were retrieved from medical records and included demographics, disease duration, lesion size, best-corrected visual acuity (BCVA), previous number of IVIs, and type of drug applied. RESULTS: A total of 35 eyes of 35 patients (76.23 years ± 7.05 years) were included, and 21 eyes (60%) responded well to SRT. The annual injection rate decreased from 6.86 before SRT to 3.46 afterward, whereas BCVA improved from 0.49 logMAR at baseline to 0.37 logMAR at final follow-up. From a morphologic point of view, CMT and SFCT decreased by 71 µm and 37 µm, respectively, at 12-month follow-up compared to baseline. Of all investigated parameters, only SFCT proved to be significant, as a higher baseline SFCT was found to be a strong negative predictor for the number of IVIs needed after SRT (regression coefficient: -0.678; P < .001). CONCLUSIONS: Baseline SFCT may help predict which patients with nAMD will respond more favorably to SRT. The authors found eyes with a thicker baseline SFCT needed fewer IVIs after SRT. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:320-328.].

Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model.

PURPOSE: This study aims to evaluate and standardize the reliability of a mobile laser indirect ophthalmoscope in the induction of choroidal neovascularization (CNV) in a mouse model. MATERIALS & METHODS: A diode laser indirect ophthalmoscope was used to induce CNV in pigmented male C57BL/6J mice. Standardization of spot size and laser intensity was determined using different aspheric lenses with increasing laser intensities applied around the optic disc. Development of CNV was evaluated 1, 5, and 14 days post laser application using fluorescein angiography (FA), histology, and choroidal flat mounts stained for the endothelial marker CD31 and FITC-dextran. Correlation between the number of laser hits to the number and size of developed CNV lesions was determined using flat mount choroid staining. The ability of intravitreally injected anti-human and anti-mouse VEGF antibodies to inhibit CNV induced by the mobile laser was evaluated. RESULTS: Laser parameters were standardized on 350 mW for 100 msec, using the 90 diopter lens to accomplish the highest incidence of Bruch's membrane rupture. CNV lesions' formation was validated on days 5 and 14 post laser injury, though FA showed leakage on as early as day 1. The number of laser hits was significantly correlated with the CNV area. CNV growth was successfully inhibited by both anti-human and mouse VEGF antibodies. CONCLUSION: The mobile laser indirect ophthalmoscope can serve as a feasible and a reliable alternative method for the CNV induction in a mouse model.

Effects of a high level of illumination before sleep at night on chorioretinal thickness and ocular biometry.

The choroid is affected by many factors. One of the factors, change in illumination has been suggested to influence choroidal thickness. However, the effects of bright light before sleep at night on the human eye are not well established. The purpose of this study was to investigate the effects of a high level of illumination in the evening on ocular measurements. Twenty-seven men with myopia spent seven consecutive nights in the sleep laboratory. During the first two nights, subjects were exposed to light at 150 lux between 20:00 and midnight. Then, for five consecutive nights, they were exposed to ambient light at 1000 lux between 20:00 and midnight. Ocular parameters and their diurnal variations were compared between the two periods and the effects of a high level of illumination were analyzed. After subjects were exposed to 1000 lux of illumination, axial length increased with borderline significance (p = 0.064). Macular volume and retinal thickness did not change. However, subfoveal choroidal thickness after exposure to 1000 lux of illumination (245.37 ± 52.84 µm) was significantly lower than that after 150 lux of illumination (268.00 ± 57.10 µm), (p < 0.001). Significant diurnal variations were found in mean keratometry (p = 0.039), intraocular pressure (IOP, p = 0.003), ocular perfusion pressure (OPP, p < 0.0001), macular volume (p = 0.019), and subfoveal choroidal thickness (p < 0.0001). A high level of illumination had significant effects on only IOP and OPP (p = 0.027 and 0.017, respectively). Bright light exposure before sleep at an intensity as high as 1000 lux reduced subfoveal choroidal thickness in healthy young men. In conclusion, diurnal variation in choroidal thickness can be affected by bright light exposure before sleep.

Juxtapapillary and circumpapillary choroidal melanoma: globe-sparing treatment outcomes with iodine-125 notched plaque brachytherapy.

PURPOSE: Managing juxtapapillary and circumpapillary choroidal melanoma with brachytherapy is challenging because of technical complications with accurate plaque placement and high radiation toxicity given tumor proximity to the optic nerve. We evaluated our center's experience using ultrasound-guided, Iodine (I)-125 notched plaque brachytherapy for treating choroidal melanoma contiguous with (juxtapapillary) and at least partially surrounding the optic disc (circumpapillary). METHODS: All cases of choroidal melanoma treated with I-125 notched plaque brachytherapy at our center from September 2003-December 2013 were retrospectively reviewed. Only patients with ≥18 months of follow-up who had lesions contiguous with the optic disc (0 mm of separation) were included. The tumor apex prescription dose was 85 Gy. Outcomes evaluated included local control, distant metastasis-free survival (DMFS), cancer-specific survival (CSS), overall survival (OS), visual acuity, and radiation toxicity. RESULTS: Thirty-four patients were included with a median follow-up of 44.1 months (range 18.2-129.0). AJCC T-category was T1 in 58.8%, T2 in 26.5%, and T3 in 14.7%. Median circumferential optic disc involvement was 50% (range 10%-100%). Eye retention was achieved in 94.1%. Actuarial 2- and 4-year rates of local recurrence were 3.1% and 7.6%, DMFS were 97.0% and 88.5%, CSS were 97.0% and 92.8%, and OS were 97.0% and 88.9%, respectively. In addition, 23.5% had visual acuity ≥20/200 at last follow-up. CONCLUSIONS: I-125 notched plaque brachytherapy provides high eye preservation rates with acceptable longer-term post-treatment visual outcomes. Based on our experience, choroidal melanoma directly contiguous with and partially encasing the optic disc may be effectively treated with this technique.

In Vivo Efficacy of an Injectable Microsphere-Hydrogel Ocular Drug Delivery System.

PURPOSE: Demonstrate in vivo that controlled and extended release of a low dose of anti-vascular endothelial growth factor (anti-VEGF) from a microsphere-hydrogel drug delivery system (DDS) has a therapeutic effect in a laser-induced rat model of choroidal neovascularization (CNV). METHODS: Anti-VEGF (ranibizumab or aflibercept) was loaded into poly(lactic-co-glycolic acid) microspheres that were then suspended within an injectable poly(N-isopropylacrylamide)-based thermo-responsive hydrogel DDS.The DDS was shown previously to release bioactive anti-VEGF for ~200 days. CNV was induced using an Ar-green laser. The four experimental groups were as follows: (i) non-treated, (ii) drug-free DDS, (iii) anti-VEGF-loaded DDS, and (iv) bolus injection of anti-VEGF. CNV lesion areas were measured based on fluorescein angiograms and quantified using a multi-Otsu thresholding technique. Intraocular pressure (IOP) and dark-adapted electroretinogram (ERG) were also obtained pre- and post-treatment (1, 2, 4, 8, and 12 weeks). RESULTS: The anti-VEGF-loaded DDS group had significantly smaller (60%) CNV lesion areas than non-treated animals throughout the study. A small transient increase in IOP was seen immediately after injection; however, all IOP measurements at all time points were within the normal range. There were no significant changes in ERG maximal response compared to pre-treatment measurements for the drug-loaded DDS, which suggests no adverse effects on retinal cellular function. CONCLUSIONS: The current study demonstrates that the DDS can effectively decrease laser-induced CNV lesions in a murine model. Controlled and extended release from our DDS achieved greater treatment efficacy using an order of magnitude less drug than what is required with bolus administration. This suggests that our DDS may provide a significant advantage in the treatment of posterior segment eye diseases.

Stereotactic radiotherapy in neovascular age-related macular degeneration: Real-life efficacy and morphological evaluation of the outer retina-choroid complex.

Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis.Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety.Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers.Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk.

Thinning of the RPE and choroid associated with T lymphocyte recruitment in aged and light-challenged mice.

PURPOSE: Thinning of the RPE and the underlying vascular layer, the choroid, is observed with age in many human eye disorders. The reasons for this thinning are ill-defined. Here, we highlight the possible role of T lymphocyte recruitment in choroidoretinal thinning in aged and light-challenged mice. METHODS: In age and light challenge models, we measured chemokine concentrations using enzyme-linked immunosorbent assay and used flow cytometry to characterize lymphocyte populations. We quantified thinning in eye immunosections and RPE65 expression using quantitative PCR. RESULTS: Age and light challenge led to increased levels of the lymphotactic protein CXCL10 alone (aging) or in conjunction with CXCL9 (light challenge). Increased numbers of CD3+ T lymphocytes, most of them CD8+ cytotoxic T lymphocytes, were also observed in the choroid and retina of old mice and following light challenge. Influx of T lymphocytes was associated with RPE and choroidal thinning and diminished expression of RPE65 mRNA, an essential enzyme of the visual cycle. CONCLUSIONS: The observations from this study suggest that cytotoxic CD8(+) T lymphocytes might participate in choroidal and RPE degeneration and that modulation of T lymphocyte recruitment might be a novel strategy to reduce choroidoretinal dysfunctions observed with age and following photo-oxidative stress.

Chlorophyllin-M: A new substance for photodynamic therapy in the retina and choroid.

BACKGROUND AND OBJECTIVE: Chlorophyllin-M is a new chlorophyll-based derivative photosensitive compound developed by our research group with easy laboratorial synthesis and ideal properties for photodynamic therapy (PDT). It is intended for clinical treatments with simple and low cost techniques and reagents. The objective of this study is to evaluate if intravenous chlorophyllin-M is able to deliver a photosensitizer to rabbit retina and rabbit choroid and promote PDT after ocular irradiation with a 660 nm LASER. METHODS: This is a pre-clinical study. Ten eyes of five pigmented Californian rabbits were included in the study. The right eyes served as the treatment group, and the left eyes served as the control group. All eyes had been ophthalmologically evaluated and were considered normal. RESULTS: Ophthalmic exam with anterior biomicroscopy, dilated fundus examination, and fluorescein angiography after the LASER procedure revealed normal anterior segment, retinal and choroid vessels occlusion, lumen narrowing, and capillary non-perfusion in the treated areas, indicating that PDT was successful in the treatment eyes group. CONCLUSION: The results of this pre-clinical study encourage future studies with this new compound. Chlorophyllin-M may become a new cost-effective agent in the retinal therapeutic arsenal.

Blue light-induced inflammatory marker expression in the retinal pigment epithelium-choroid of mice and the protective effect of a yellow intraocular lens material in vivo.

Oxidative stress in the retinal pigment epithelium (RPE) is a well-accepted pathogenic change in vision-threatening diseases such as age-related macular degeneration. One source of oxidative stress is excessive light exposure, which causes excessive activation of the visual cycle. Because short wavelength light (blue light) has more energy, it is reported to be more harmful to photoreceptor cells than the other wavelengths of light. However, the biological effect of blue light in the RPE of living animals and the protective effect of a yellow intraocular lens (IOL) material that blocks blue light is still obscure. Therefore, we compared the pathogenic effect in the RPE-choroid complexes of mice exposed to light in a box made of a clear or a yellow IOL material. We measured the level of reactive oxygen species (ROS) using 2', 7'-dichlorodihydrofluorescein diacetate, the mRNA levels of inflammatory cytokines and a macrophage marker by real-time polymerase chain reaction, and the protein level of monocyte chemotactic protein-1 (MCP-1) by ELISA. The ROS level after light exposure was suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. In parallel, all the inflammatory cytokines that we measured and a macrophage marker were also suppressed in the RPE-choroids of light-exposed mice in the yellow IOL material box. Therefore, a yellow IOL material suppressed, and thus blue light exacerbated, the increase in the ROS level and inflammatory cytokine expression as well as macrophage recruitment in the RPE-choroid in vivo after light exposure.