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Purpose: To report a previously unreported presentation of advanced geographic atrophy of the macula mimicking nonneovascular (dry) age-related macular degeneration in a patient with light chain deposition disease., Methods: Ocular examination included dilated fundus examination, fundus autofluorescence, full-field electroretinography, and spectral domain optical coherence tomography., Patients: Single-patient case report., Results: Dilated fundus examination demonstrated diffuse loss of the retinal pigment epithelium in a geographic atrophy pattern in the macula and drusenlike deposits localized to the outer retina and retinal pigment epithelium. There were no signs of choroidal neovascularization or retinal pigment epithelium detachments. Fundus autofluorescence demonstrated wide areas of retinal pigment epithelium loss. Full-field electroretinography was normal. Spectral domain optical coherence tomography displayed atrophy of the outer retinal layers., Discussion: This is the first documented case of drusenlike deposits and maculopathy in a patient with light chain deposition disease that mimics advanced geographic atrophy that is typically observed in nonneovascular age-related macular degeneration. Physicians should be aware of the macular changes that can be associated with light chain deposition disease, and patients with light chain deposition disease should be regularly evaluated for associated macular disease., Competing Interests: None of the authors have any conflicting interests to disclose.

Objective: To evaluate intraretinal anatomy in patients with exudative age-related macular degeneration (AMD) using high-speed ultrahigh resolution optical coherence tomography (hsUHR-OCT) before and 1 month after intravitreal injection of ranibizumab., Design: Retrospective case series., Participants: Twelve eyes of 12 patients., Methods: A broad bandwidth superluminescent diode laser light source and spectral/Fourier domain signal detection were used to create a prototype hsUHR-OCT instrument with 3.5 mum axial image resolution and approximately 25,000 lines/second acquisition speed. Twelve eyes of 12 patients with exudative AMD were imaged with hsUHR-OCT before and 1 month after intravitreal ranibizumab injection. High pixel density and raster-scanned 3-dimensional (3D) OCT data sets were generated. Three-dimensional imaging software was used to calculate subretinal/retinal pigment epithelium fluid volume and volume of the fibrovascular lesion., Main Outcome Measures: Qualitative and quantitative analysis of hsUHR-OCT images and 3D data sets., Results: All eyes had some degree of normalization of macular contour after intravitreal ranibizumab. The inner/outer photoreceptor segment junction visualized on hsUHR-OCT was discontinuous, overlying the fibrovascular lesion in all 12 of 12 eyes both before and after treatment; 9 of 12 eyes had focal areas of thinning of the outer nuclear layer, which remained after treatment. Volumetric measurements were possible in 8 of 12 eyes with 3D-rendering software. Fibrovascular lesion volume did not change significantly after treatment., Conclusions: hsUHR-OCT is capable of unprecedented imaging speed and resolution, making it a valuable instrument in measuring in vivo intraretinal pathology. All 12 eyes had some normalization of macular contour. Fibrovascular lesion volume did not change significantly 1 month after treatment, suggesting that ranibizumab does not cause much initial regression of preexisting neovascular tissue. Photoreceptor abnormalities remained in all patients after treatment of wet AMD, suggesting that although ranibizumab improves overall retinal architecture, some photoreceptor damage may be irreversible., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Aims: To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD)., Methods: A high-speed, 3.5 mum resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated., Results: Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images., Conclusions: Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.

North Carolina macular dystrophy is characterized by nonprogressive atrophy of the choroid, choriocapillaris, and the retinal pigment epithelial layer. The characteristic retinal findings, ranging from scattered drusen to a posterior staphyloma, have been reported as early as infancy and usually reach their greatest magnitude in the second decade of life. Herein, we describe a case of a 3-year-old boy with a documented family history of North Carolina macular dystrophy who presented with a subfoveal choroidal neovascular membrane in addition to the macular dystrophic changes.

Aim: Off-label intravitreal injections of bevacizumab (Avastin) have been given for the treatment of neovascular and exudative ocular diseases since May 2005. Since then, the use of intravitreal bevacizumab has spread worldwide, but the drug-related adverse events associated with its use have been reported only in a few retrospective reviews. The International Intravitreal Bevacizumab Safety Survey was initiated to gather timely information regarding adverse events from doctors around the world via the internet., Methods: An internet-based survey was designed to identify adverse events associated with intravitreal bevacizumab treatment. The survey web address was disseminated to the international vitreoretinal community via email. Rates of adverse events were calculated from participant responses., Results: 70 centres from 12 countries reported on 7113 injections given to 5228 patients. Doctor-reported adverse events included corneal abrasion, lens injury, endophthalmitis, retinal detachment, inflammation or uveitis, cataract progression, acute vision loss, central retinal artery occlusion, subretinal haemorrhage, retinal pigment epithelium tears, blood pressure elevation, transient ischaemic attack, cerebrovascular accident and death. None of the adverse event rates exceeded 0.21%., Conclusion: Intravitreal bevacizumab is being used globally for ocular diseases. Self-reporting of adverse events after intravitreal bevacizumab injections did not show an increased rate of potential drug-related ocular or systemic events. These short-term results suggest that intravitreal bevacizumab seems to be safe.

Aim: To describe the appearance of the non-exudative forms of age related macular degeneration (AMD) as imaged by ultrahigh resolution optical coherence tomography (UHR-OCT)., Methods: A UHR-OCT ophthalmic imaging system, which utilises a femtosecond laser light source capable of approximately 3 mum axial resolution, was employed to obtain retinal cross sectional images of patients with non-exudative AMD. Observational studies of the resulting retinal images were performed., Results: 52 eyes of 42 patients with the clinical diagnosis of non-exudative AMD were imaged using the UHR-OCT system. 47 of the 52 (90%) eyes had the clinical diagnosis of drusen and/or retinal pigment epithelial (RPE) changes. In these patients, three patterns of drusen were apparent on UHR-OCT: (1) distinct RPE excrescences, (2) a saw toothed pattern of the RPE, and (3) nodular drusen. On UHR-OCT, three eyes (6%) with a clinical diagnosis of non-exudative AMD had evidence of fluid under the retina or RPE. Two of these three patients had findings suspicious for subclinical choroidal neovascularisation on UHR-OCT., Conclusion: With the increased resolution of UHR-OCT compared to standard OCT, the involvement of the outer retinal layers are more clearly defined. UHR-OCT may allow for the detection of early exudative changes not visible clinically or by angiography.

Purpose: To examine the molecular genetic basis and phenotypic characteristics of an unusual late-onset autosomal dominant macular dystrophy with features of age-related macular degeneration (AMD) in a large family (SUNY901), by using linkage and mutation analyses., Methods: Blood samples were collected from 17 affected members, 17 clinically unaffected members, and 5 unrelated spouses. Clinical analyses included a review of medical history and standard ophthalmic examination with fundus photography, fluorescein angiography, and electroretinography. Linkage and haplotype analyses were performed with microsatellite markers. Mutation analysis was performed by amplification of exons followed by sequencing., Results: A wide spectrum of clinical phenotypes including exudative and nonexudative maculopathy was observed, with onset in the late fifth decade. Linkage analysis excluded most of the previously known maculopathy loci. Markers D6S1604 (Z(max) of 3.18 at theta = 0), and D6S282 (Z(max) of 3.18 at theta = 0) gave significant positive LOD scores and haplotype analysis localized the disease gene to a 9-centimorgan (cM) interval between markers D6S1616 and D6S459. Mutation analysis excluded the GUCA1A and GUCA1B genes and revealed a missense mutation in the RDS/peripherin gene leading to a Tyr141Cys substitution. A phenotype and haplotype comparison between this and a separate family with the Tyr141Cys mutation suggested the presence of a common ancestral haplotype., Conclusions: The RDS mutation in codon 141 is associated with an unusual AMD-like late-onset maculopathy. An apparent selective bias was noted favoring the transmission of the mutant allele. These observations broaden the spectrum of phenotypes associated with RDS gene mutations.

Transpupillary thermotherapy (TTT) is a subthreshold, low irradiance, long exposure duration, large spot size, infrared diode laser protocol. Retinal temperature increases in TTT for choroidal neovascularization (CNV) are substantially lower than those in conventional short-pulse photocoagulation, but they are maintained for 60 seconds to achieve therapeutic results. Treatment power is adjusted for retinal lesion size, chorioretinal pigmentation, macular elevation and media clarity. TTT uses 810-nm diode laser infrared radiation, which has no significant retinal phototoxicity. A parfocal laser delivery system is required to assure uniformity of irradiance across large diameter treatment spots. Relative contraindications for TTT include dense subretinal hemorrhage, prior focal photocoagulation and serous RPE detachment. Adverse events are rare, and include decreased vision and retinal arteriole occlusion. Randomized, prospective multi-center trials are underway to compare the results of TTT for occult CNV in age-related macular degeneration to the natural history of the disorder. Imaging, electrophysiologic or thermometric techniques may ultimately provide intra-operative or post-operative monitoring to assure the adequacy of TTT for CNV, despite the absence of ophthalmoscopically visible lesions.

Objective: To provide a biophysical foundation for using transpupillary thermotherapy (TTT) to manage choroidal neovascularization in age-related macular degeneration (ARMD)., Methods: Retinal temperature rise in laser therapy is proportional to retinal irradiance (laser power/area) for a particular spot size, exposure duration, and wavelength. TTT is a low irradiance, large spot size, prolonged exposure (long-pulse), infrared laser photocoagulation protocol. Results from an experimentally confirmed, finite element model of retinal light absorption and heat conduction are used to analyze laser parameter selection and its consequences. Results from apoptosis, heat shock protein and hyperthermia research are used to examine how chorioretinal damage from clinical procedures might be reduced., Results: Chorioretinal thermal equilibration occurs during long-pulse TTT photocoagulation. Retinal temperature increases are similar in the RPE where laser radiation absorption is significant and in the adjacent neural retina where there is negligible radiation absorption. For parameters used to treat occult choroidal neovascularization in lightly-pigmented fundi (800-mW, 810-nm, 3-mm retinal spot diameter, 60-sec exposure duration), the maximum chorioretinal temperature elevation is calculated to be roughly 10 degrees C, significantly lower than the 20 degrees C temperature elevations measured in threshold, conventional short-pulse retinal photocoagulation., Conclusions: To achieve a preselected temperature rise, TTT laser power must be increased or decreased in proportion to the diameter rather than the area of the laser spot. Clinical power settings should be adjusted for fundus pigmentation and media clarity because both of these factors affect absorbed retinal irradiance and thus retinal temperature rise. Noninvasive thermal dosimetry currently is unavailable for clinical retinal photocoagulation, but potential thermometric techniques include MRI, liposomal-encapsulated dyes, multispectral imaging or reflectometry, and subretinal or episcleral thermometry. TTT may be useful not only as independent therapy, but also as an adjunct to PDT, antiangiogenic drugs and ionizing radiation therapy in the management of neovascular ARMD. Low temperature, long-pulse photocoagulation is a potential strategy for decreasing neural retinal damage in subsequent TTT or short-pulse photocoagulation and perhaps even for treating glaucoma or retinal degenerations.

Objective: To evaluate the efficacy of transpupillary thermotherapy for the treatment of occult subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration., Design: A retrospective, noncomparative case series., Participants: Sixteen eyes of 15 consecutive patients who presented with occult subfoveal choroidal neovascularization secondary to age-related macular degeneration., Intervention: After informed consent was obtained, 16 eyes of 15 patients were treated with transpupillary thermotherapy. All patients underwent pretreatment fluorescein angiography and were deemed untreatable by the Macular Photocoagulation Study standard. Transpupillary thermotherapy was delivered using a diode laser at 810 nm. A variable spot size of 1.2 mm, 2.0 mm, or 3.0 mm was used depending on the size of CNV. The diode laser was delivered through a contact lens, and treatment was initiated in one spot for 60 seconds' duration at a power range between 360 and 1000 mW. The end point was an area of no visible color change to a light-gray appearance., Main Outcome Measures: In all eyes, outcome was assessed by Snellen chart visual acuity and clinical examination. In 10 of 16 eyes, preoperative and postoperative fluorescein angiography and optical coherence tomography were available. In the remaining 6 of 16 eyes, exudation was measured by postoperative clinical examination alone., Results: Three eyes (19%) showed a two-or-more-line improvement in visual acuity over a period of 6 to 25 months. Mean follow-up was 13 months. Visual acuity remained stable (no change or one-line improvement) in nine treated eyes (56%). The remaining four eyes (25%) showed a decline (equal to one-line worsening or greater) in visual acuity. Fifteen eyes (94%) demonstrated decreased exudation on fluorescein angiography, optical coherence tomography, and/or clinical examination., Conclusions: Transpupillary thermotherapy shows no deleterious side effects in treating occult subfoveal choroidal neovascularization. A randomized, prospective study is necessary to evaluate treatment efficacy.

Purpose: Indocyanine green (ICG) angiography may improve visualization of choroidal neovascularization (CNV) associated with serous retinal pigment epithelial detachment (RPED) in age-related macular degeneration (AMD). The features of ICG hyperfluorescence associated with serous RPED and therapeutic effect of ICG-directed laser photocoagulation in eyes with serous RPED is evaluated., Design: Retrospective review of all simultaneous fluorescein/ICG angiograms (n = 918) performed over an 18-month period to identify 44 eyes in 39 patients with serous RPED secondary to AMD on fluorescein angiography., Participants: Thirty-nine patients with AMD, aged 53 to 89 years, participated., Intervention: Eyes were nonrandomly treated with ICG-directed laser photocoagulation or observation., Main Outcome Measures: Characteristics of ICG hyperfluorescence associated with a serous RPED are reviewed. Final visual acuity and anatomic appearance of the serous RPED are given., Results: Twenty-three (52%) of the 44 eyes had an isolated serous RPED without obvious CNV, and 21 (48%) of the 44 eyes had a serous RPED associated with occult CNV on fluorescein angiography. Indocyanine green angiography demonstrated underlying CNV in 19 eyes (83%) with an isolated serous RPED and in all 21 eyes (100%) with serous RPED and occult CNV. The pattern of ICG hyperfluorescence revealed focal CNV in 15 eyes and plaque CNV in 4 eyes with an isolated serous RPED. In eyes with serous RPED and occult CNV, focal CNV and plaque CNV were noted with ICG in 8 and 13 eyes, respectively. No follow-up was available for two eyes. Twenty eyes were treated with ICG-directed laser photocoagulation. In these eyes, the visual acuity remained stable in 6 eyes (30%) and decreased in 14 eyes (70%). Twenty-two eyes were observed, and the visual acuity remained stable in 8 (36%), improved in 2 (9%), and decreased in 12 eyes (55%)., Conclusions: Although ICG angiography may enhance visualization of CNV associated with serous RPED in AMD, ICG-directed laser treatment did not appear to improve visual acuity when compared with observed eyes in this series.

Objective: The authors used optical coherence tomography (OCT), a new technique for cross-sectional imaging of the retina, to morphologically study eyes with nonexudative and exudative age-related macular degeneration (AMD). In patients with untreated exudative AMD, OCT was compared with fluorescein angiography in the identification and classification of choroidal neovascularization (CNV)., Methods: Optical coherence tomography imaging is analogous to ultrasound, except that the use of light rather than sound enables higher longitudinal resolution with a noncontact and noninvasive measurement. Optical coherence tomography was performed on 391 patients with the clinical diagnosis of AMD and was compared with conventional clinical examination to establish the cross-sectional morphology of different lesions and to develop a classification scheme for CNV. Optical coherence tomograms and fluorescein angiograms then were reviewed and correlated independently in 90 eyes of 86 patients who had exudative AMD without previous laser treatment., Results: Pigmentary changes, soft drusen, and detachments of the neurosensory retina and retinal pigment epithelium all had distinct presentations on OCT. Subretinal and intraretinal fluid caused changes in retinal thickness or elevation that could be quantified directly from the images. Choroidal neovascularization was evident in the tomograms as a thickening and fragmentation of a reflective layer, which corresponded to the retinal pigment epithelium and choriocapillaris. Changes in the reflection from this layer were observed during the progression of neovascularization, and after laser photocoagulation treatment. Classic CNV consistently presented with well-defined boundaries on OCT, whereas occult CNV had a variable cross-sectional appearance., Conclusions: Optical coherence tomography was useful in quantitatively evaluating subretinal and intraretinal fluid, assessing possible subfoveal involvement of neovascularization, and in monitoring CNV before and after laser photocoagulation. Optical coherence tomography was unable to detect CNV beneath serous pigment epithelial detachments. Optical coherence tomography may have potential in accurately defining the boundaries in a subset of angiographically occult CNV.

Background and Objective: Recurrence of choroidal neovascular membranes (CNV) occurs frequently following laser photocoagulation. Recurrent CNV can be difficult to treat because they may not be well defined by fluorescein angiography., Patients and Methods: The fluorescein and indocyanine green (ICG) angiograms of 58 eyes of 57 patients who presented with clinically suspected recurrence were evaluated retrospectively., Results: In 14 eyes (24%), a well-defined recurrent CNV could be identified by evaluating the fluorescein angiogram. In 6 (14%) of the remaining 44 eyes, a well-defined recurrent CNV was identifiable by ICG angiography., Conclusion: A role for ICG angiography in the care of patients with suspected recurrent CNV is discussed.