BACILLARY LAYER DETACHMENT AFTER PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To report the clinical and optical coherence tomography findings of a patient with chronic central serous chorioretinopathy who developed a short-term bacillary layer detachment after photodynamic therapy (PDT). METHODS: A 56-year-old man presented with metamorphopsia and 20/100 visual acuity in his right eye. He was diagnosed with active, chronic central serous chorioretinopathy based on clinical findings and multimodal imaging. His visual problems and retinal findings persisted for 3 months before he was treated with half-fluence, half-dose verteporfin PDT. RESULTS: The patient had a prominent decrease in his vision postoperatively. Two days after treatment, multimodal imaging showed a marked increase in exudation that merged preoperative neurosensory retinal detachments. A prominent subfoveal bacillary layer detachment was also present. The subretinal fluid and bacillary layer detachment resolved over the next 8 weeks, with a return of visual acuity to its baseline level and normalization of retinal structures except for a small zone of subfoveal ellipsoid zone and interdigitation zone disruption. CONCLUSION: Half-fluence, half-dose verteporfin PDT caused a fulminant increase in subretinal fluid and an associated subfoveal bacillary layer detachment. We hypothesize that chronic central serous chorioretinopathy-related chorioretinal dysfunction contributed to the severe PDT-induced local inflammatory reaction that caused the patient's bacillary layer detachment. Hyperacute choroidal exudation too fulminant for containment in subretinal space extended into and exceeded photoreceptor inner segment tensile strength, cleaving the myoid layer and/or dissecting it from the ellipsoid layer. This finding broadens the causality spectrum of bacillary layer detachments and vision losses that can follow PDT.

Half-Fluence, Half-Dose Photodynamic Therapy: Less Direct Damage but More Inflammation?

Objective: To present clinical findings and multimodal imaging of three patients who developed bacillary layer detachments (BALADs) shortly after half-fluence, half-dose (HFHD) verteporfin photodynamic therapy (PDT). Methods: Retrospective observational case series. Three patients were treated with HFHD-PDT for (1) macular neovascularisation five years after resolved central serous chorioretinopathy (CSC), (2) persistent serous retinal detachment (SRD) from chronic CSC, and (3) neovascular age-related macular degeneration with persistent SRD despite intravitreal anti-VEGF therapy. Results: Each patient developed a BALAD after HFHD-PDT. Acute fulminant exudation caused subretinal fluid expansion into the inner photoreceptor layer, cleaving myoid from ellipsoid zones in the central macula. Subretinal fluid and the BALADs subsequently resolved over 6-8 weeks. Conclusions: The subretinal fluid and BALAD following HFHD-PDT were transient and did not cause photoreceptor damage over a 6-month follow-up period. We speculate that the reduced-impact HFHD protocol decreases direct tissue damage but increases proinflammatory cytokines. The long-term pathophysiological consequences of the resolved BALADs are unknown.

Scanning laser ophthalmoscopy retroillumination: applications and illusions.

Scanning laser ophthalmoscopes (SLOs) are used widely for reflectance, fluorescence or autofluorescence photography and less commonly for retroillumination imaging. SLOs scan a visible light or near-infrared radiation laser beam across the retina, collecting light from each retinal spot as it's illuminated. An SLO's clinical applications, image contrast and axial resolution are largely determined by an aperture overlying its photodetector. High contrast, reflectance images are produced using small diameter, centered apertures (confocal apertures) that collect retroreflections and reject side-scattered veiling light returned from the fundus. Retroillumination images are acquired with annular on-axis or laterally-displaced off-axis apertures that capture scattered light and reject the retroreflected light used for reflectance imaging. SLO axial resolution is roughly 300 µm, comparable to macular thickness, so SLOs cannot provide the depth-resolved chorioretinal information obtainable with optical coherence tomography's (OCT's) 3 µm axial resolution. Retroillumination highlights and shades the boundaries of chorioretinal tissues and abnormalities, facilitating detection of small drusen, subretinal drusenoid deposits and subthreshold laser lesions. It also facilitates screening for large-area chorioretinal irregularities not readily identified with other en face retinal imaging modalities. Shaded boundaries create the perception of lesion elevation or depression, a characteristic of retroillumination but not reflectance SLO images. These illusions are not reliable representations of three-dimensional chorioretinal anatomy and they differ from objective OCT en face topography. SLO retroillumination has been a useful but not indispensable retinal imaging modality for over 30 years. Continuing investigation is needed to determine its most appropriate clinical roles in multimodal retinal imaging.

The Blue Light Hazard Versus Blue Light Hype.

PURPOSE: The blue light hazard is the experimental finding that blue light is highly toxic to the retina (photic retinopathy), in brief abnormally intense exposures, including sungazing or vitreoretinal endoillumination. This term has been misused commercially to suggest, falsely, that ambient environmental light exposure causes phototoxicity to the retina, leading to age-related macular degeneration (AMD). We analyze clinical, epidemiologic, and biophysical data regarding blue-filtering optical chromophores. DESIGN: Perspective. METHODS: Analysis and integration of data regarding the blue light hazard and blue-blocking filters in ophthalmology and related disciplines. RESULTS: Large epidemiologic studies show that blue-blocking intraocular lenses (IOLs) do not decrease AMD risk or progression. Blue-filtering lenses cannot reduce disability glare because image and glare illumination are decreased in the same proportion. Blue light essential for optimal rod and retinal ganglion photoreception is decreased by progressive age-related crystalline lens yellowing, pupillary miosis, and rod and retinal ganglion photoreceptor degeneration. Healthful daily environmental blue light exposure decreases in older adults, especially women. Blue light is important in dim environments where inadequate illumination increases risk of falls and associated morbidities. CONCLUSIONS: The blue light hazard is misused as a marketing stratagem to alarm people into using spectacles and IOLs that restrict blue light. Blue light loss is permanent for pseudophakes with blue-blocking IOLs. Blue light hazard misrepresentation flourishes despite absence of proof that environmental light exposure or cataract surgery causes AMD or that IOL chromophores provide clinical protection. Blue-filtering chromophores suppress blue light critical for good mental and physical health and for optimal scotopic and mesopic vision.

COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps.

BACKGROUND: COL4A3, COL4A4, and COL4A5 are the only collagen genes that have been implicated in inherited nephropathies in humans. However, the causative genes for a number of hereditary multicystic kidney diseases, myopathies with cramps, and heritable intracranial aneurysms remain unknown. METHODS: We characterized the renal and extrarenal phenotypes of subjects from three families who had an autosomal dominant hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC), which we propose is a syndrome. Linkage studies involving microsatellite markers flanking the COL4A1-COL4A2 locus were performed, followed by sequence analysis of COL4A1 complementary DNA extracted from skin-fibroblast specimens from the subjects. RESULTS: We identified three closely located glycine mutations in exons 24 and 25 of the gene COL4A1, which encodes procollagen type IV alpha1. The clinical renal manifestations of the HANAC syndrome in these families include hematuria and bilateral, large cysts. Histologic analysis revealed complex basement-membrane defects in kidney and skin. The systemic angiopathy of the HANAC syndrome appears to affect both small vessels and large arteries. CONCLUSIONS: COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.

Does context or color improve object recognition in patients with low vision?

Most studies on people with age-related macular degeneration (AMD) have been focused on investigations of low-level processes with simple stimuli like gratings, letters, and in perception of isolated faces or objects. We investigated the ability of people with low vision to analyze more complex stimuli like photographs of natural scenes. Fifteen participants with AMD and low vision (acuity on the better eye <20/200) and 11 normally sighted age-matched controls took part in the study. They were presented with photographs of either colored or achromatic gray level scenes in one condition and with photographs of natural scenes versus isolated objects extracted from these scenes in another condition. The photographs were centrally displayed for 300 ms. In both conditions, observers were instructed to press a key when they saw a predefined target (a face or an animal). The target was present in half of the trials. Color facilitated performance in people with low vision, while equivalent performance was found for colored and achromatic pictures in normally sighted participants. Isolated objects were categorized more accurately than objects in scenes in people with low vision. No difference was found for normally sighted observers. The results suggest that spatial properties that facilitate image segmentation (e.g., color and reduced crowding) help object perception in people with low vision.

Recognition of facial emotion in low vision: a flexible usage of facial features.

Age-related macular degeneration (AMD) is a major cause of visual impairment in people older than 50 years in Western countries, affecting essential tasks such as reading and face recognition. Here we investigated the mechanisms underlying the deficit in recognition of facial expressions in an AMD population with low vision. Pictures of faces displaying different emotions with the mouth open or closed were centrally displayed for 300 ms. Participants with AMD with low acuity (mean 20/200) and normally sighted age-matched controls performed one of two emotion tasks: detecting whether a face had an expression or not (expressive/non expressive (EXNEX) task) or categorizing the facial emotion as happy, angry, or neutral (categorization of expression (CATEX) task). Previous research has shown that healthy observers are mainly using high spatial frequencies in an EXNEX task while performance at a CATEX task was preferentially based on low spatial frequencies. Due to impaired processing of high spatial frequencies in central vision, we expected and observed that AMD participants failed at deciding whether a face was expressive or not but categorized normally the emotion of the face (e.g., happy, angry, neutral). Moreover, we observed that AMD participants mostly identified emotions using the lower part of the face (mouth). Accuracy did not differ between the two tasks for normally sighted observers. The results indicate that AMD participants are able to identify facial emotion but must base their decision mainly on the low spatial frequencies, as they lack the perception of finer details.

Comparison of laser beam intensity profiles produced by photodynamic therapy (PDT) and transpupillary thermotherapy (TTT) lasers.

BACKGROUND AND OBJECTIVES: For photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) lasers, long irradiation time (typically 1 minute or longer) is used and a large area of retina is treated. Consequently, the power stability but also the light distribution within the laser beam plays a major role. This study aimed to evaluate beam intensity profiles produced by several PDT and TTT lasers. STUDY DESIGN/MATERIALS AND METHODS: A beam profile analyzer (Cohu 4812 camera connected to a LPA-300PC, Spiricon, Logan, UT) was used to compare the beam profiles of PDT lasers: OPAL (Lumenis, USA); ACTIVIS (Quantel Medical, France), VISULAS (Zeiss, Germany). Spots of 2, 3, 4, and 5 mm were tested with each laser. Similarly, TTT lasers: OCULIGHT SLx (Iridex, CA) and IRIDIS trade mark (Quantel Medical, France) were evaluated with 2 and 3 mm spot diameter and power ranging from 200 to 1,000 mW. RESULTS: PDT lasers: OPAL had a "top hat" and homogeneous profile whatever the spot size. Numerous micro-spikes and micro-nadirs of power were observed with the ACTIVIS and the VISULAS. TTT lasers: for the IRIDIS the beam shape was rather gaussian, but the homogeneity was reduced by micro-spikes of power. With the OCULIGHT Slx the beam shape was rather top hat and only few micro-spikes or micro-nadirs of power could be disclosed. DISCUSSION: The literature tends to prove that the shape and homogeneity of the beam profile could play a role on the efficacy of the treatment. CONCLUSION: Since PDT and TTT lasers display different beam profiles, this parameter should be carefully evaluated when performing clinical evaluations of PDT or TTT treatments.

Transpupillary thermotherapy (TTT) with short duration laser exposures induce heat shock protein (HSP) hyperexpression on choroidoretinal layers.

BACKGROUND AND OBJECTIVES: To assess a choroidal heat shock protein hyperexpression after transpupillary thermotherapy (TTT) performed with exposures shorter than 60 seconds. STUDY DESIGN/MATERIALS AND METHODS: Nine male pigmented rabbits were anesthetized and TTT was performed on their right eye with a 810 nm diode laser (Iridis, Quantel-Medical (France)) (spot size: 1.3 mm). Three exposure durations (60, 30, or 15 seconds) were used with three ranges of power for each duration ("high," "mild," or "low"). A series of laser impacts was delivered to the posterior pole of the retina. Left eyes were used as controls. Twenty-four hours after laser irradiation, the animals were killed and histological study was performed on chorioretinal layers. Tissue samples were fixed in formalin and embedded in paraffin. A monoclonal antibody was used to detect Hsp70 immunoreactivity (mouse IgGl, SPA-810, Stress Gen, Victoria, BC, Canada), followed by a biotinylated goat anti-mouse antibody (Dako, Glostrup, Denmark), revealed by the avidin-biotin complex (Vectastain kit, Vector Laboratries, Burlingame, CA, USA) and the AEC chromogen. Retinal structures were further identified by HES coloration. RESULTS: During the experiments, the laser spots were not visible except for the strongest "high" powers for each exposure duration, where a whitening was discernable at the end of the laser exposures. A strong HSP70 immunoreactivity was detected in choroidal, non-pigmented cells for laser exposures lasting 60, 30, or 15 seconds with "mild" laser powers. On the contrary, rare HSP hyperexpression was detected with "high" or "low" laser powers lasting 60, 30, or 15 seconds. No HSP-70 immunoreactivity was detected on control eyes nor outside of the irradiated zones of treated eyes. CONCLUSIONS: Transpupillary laser irradiation lasting 15, 30, or 60 seconds induces an hyperexpression of HSP on choroidal layers. This could be a basis for the use of TTT with "short" laser exposures.