Atrophic Macular Degeneration Research Articles

Physiological vitreous changes may contribute to the pathogenesis of atrophic and neovascular macular degeneration

Physiological vitreous changes may contribute to the pathogenesis of atrophic and neovascular macular degeneration

Visual and accommodative outcomes 1 year after implantation of an accommodating intraocular lens based on a new concept

To evaluate visual outcomes and accommodative gains 1 year after implantation of the NuLens accommodating intraocular lens (IOL). Department of Refractive Surgery, Vissum Corp., Alicante, Spain. This study comprised patients with cataract and atrophic macular degeneration. In each patient, the accommodating IOL was implanted in the eye with the worse visual acuity. At the 12-month follow-up visit, visual acuity and accommodation were measured to determine the efficacy of the IOL. Ultrasound biomicroscopy was used to measure accommodative amplitude. Ten eyes of 10 patients were evaluated. The mean number of lines patients could read increased from 1.0 preoperatively to 3.8 lines 6 months postoperatively, indicating improvement in uncorrected near visual acuity after IOL implantation. The mean change in cross-section measurements of the IOL was 0.06 mm at 1 month; the value peaked at 3 months (0.21 mm), after which it decreased steadily, becoming stable at 9 months (0.09 mm, which is equivalent to 10.00 diopters [D] of accommodation). Corrected near visual acuity improved slightly (0.7 Jaeger lines) at 12 months, with the best reading distance at 10 cm. These results suggest that the near and distance visual acuities were approximately equal and, therefore, the IOL can produce accommodation of 10.00 D. The accommodation mechanism of the IOL can produce an ocular power variation of 10.00 D. Near visual acuity improved without compromising distance visual acuity.

RPGR ORF15 genotype and clinical variability of retinal degeneration in an Australian population

Background:Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are estimated to cause up to 20% of all Caucasian retinitis pigmentosa and up to 75% of cases of X-Linked RP...

RPE transplantation and its role in retinal disease

Retinal pigment epithelial (RPE) transplantation aims to restore the subretinal anatomy and re-establish the critical interaction between the RPE and the photoreceptor, which is fundamental to sight. The field has developed over the past 20 years with advances coming from a large body of animal work and more recently a considerable number of human trials. Enormous progress has been made with the potential for at least partial restoration of visual function in both animal and human clinical work. Diseases that have been treated with RPE transplantation demonstrating partial reversal of vision loss include primary RPE dystrophies such as the merTK dystrophy in the Royal College of Surgeons (RCS) rat and in humans, photoreceptor dystrophies as well as complex retinal diseases such as atrophic and neovascular age-related macular degeneration (AMD). Unfortunately, in the human trials the visual recovery has been limited at best and full visual recovery has not been demonstrated. Autologous full-thickness transplants have been used most commonly and effectively in human disease but the search for a cell source to replace autologous RPE such as embryonic stem cells, marrow-derived stem cells, umbilical cord-derived cells as well as immortalised cell lines continues. The combination of cell transplantation with other modalities of treatment such as gene transfer remains an exciting future prospect. RPE transplantation has already been shown to be capable of restoring the subretinal anatomy and improving photoreceptor function in a variety of retinal diseases. In the near future, refinements of current techniques are likely to allow RPE transplantation to enter the mainstream of retinal therapy at a time when the treatment of previously blinding retinal diseases is finally becoming a reality.

Microincisional cataract surgery and Thinoptx rollable intraocular lens implantation

Microincisional cataract surgery is a safe procedure with a very short learning period for an experienced cataract surgeon and rollable ultrathin intraocular lenses eliminate the need for enlargement of corneal incision. The purpose of the study was to evaluate the safety and efficacy of cataract surgery through a corneal microincision and implantation of rollable ultrathin intraocular lenses. The setting was Dokuz Eylul University Medical Faculty, Ophthalmology Department, Izmir, Turkey and SSK Okmeydani Hospital, Ophthalmology Clinic, Istanbul, Turkey. Ninety eyes in 85 patients were operated on through clear corneal microincisions with sleeveless phacoemulsification and rollable intraocular lenses were implanted. Forty-six of the patients were men and 39 were women between the ages of 27 and 83, with a mean of 51 years. Two eyes had atrophic senile macular degeneration, 4 eyes had nonspecific retinal pigment epithelial changes with chorioretinal atrophy, and 4 patients had diabetes mellitus without retinopathy. Three eyes had posterior capsular opacifications of unknown etiology. Two eyes had primary open angle glaucoma (PAAG) with cup to disc ratios of about 0.5. Three eyes had dense nuclear sclerosis of grade 4 with very low visibility of retinal structures. Other patients had no ocular or systemic pathology other than nuclear/corticonuclear cataract of grade 2-3. Uncorrected and best spectacle-corrected distance and near visual acuities, keratometric values, and refractive status were noted preoperatively and 1 week, 1 month, and 6 months postoperatively. Statistical analysis of keratometric changes between preoperative and postoperative findings was performed using the paired samples t test. At 6 months postoperatively, 1 patient had a best spectacle-corrected visual acuity (BSCVA) of 0.2, the patient with atrophic senile macular degeneration. The rest of the eyes achieved a BSCVA of 0.63 or better. At 6 months postoperatively, 55 (61.11%) eyes had uncorrected visual acuities (UCVA) equal to or better than 0.8 and 83 (92.22%) eyes had BSCVA equal to or better than 0.8 according to the Snellen chart. The mean postoperative corneal astigmatisms at 1 week, 1 month, and 6 months were 0.69+/-0.43 D, 0.66+/-0.46 D and 0.65+/-0.48 D respectively. Statistical analysis revealed a significant change in corneal astigmatisms at the 1st week visit (p<0.05), but not at the 1st and 6th month visits (p>0.05) compared with preoperative findings. Based on the limited data in the literature and in this study, it is not possible to make concrete decisions about the benefits and disadvantages of the ThinOptx IOL for longer durations. Intraoperatively, this IOL apparently eliminates the need for enlargement of the corneal incision during implantation. However, the statistical insignificance of induced astigmatisms after microincisions and classical phacoincisions should also be taken into consideration. We conclude that ThinOptx IOL is a pioneering intraocular lens implant that will contribute to the exciting future of cataract refractive surgical procedures. However, both clinical and laboratory investigations are needed to clearly describe the long-term effectiveness of this new rollable IOL.

ACQUIRED COLOR BLINDNESS IN AN ELDERLY MALE PATIENT FROM RECURRENT METASTATIC PROSTATE CANCER

ACQUIRED COLOR BLINDNESS IN AN ELDERLY MALE PATIENT FROM RECURRENT METASTATIC PROSTATE CANCER

Retinotopic mapping of the visual cortex using functional magnetic resonance imaging in a patient with central scotomas from atrophic macular degeneration

Purpose To describe retinotopic mapping of the visual cortex when a central scotoma is present. Design Single observational case report. Methods Scanning laser ophthalmoscope perimetry was used to define the site and stability of fixation and the area of dense scotoma. Functional magnetic resonance imaging of the visual cortex was performed while the patient viewed an expanding annular stimulus. Results Retinotopic mapping of the visual cortex for a patient with a horseshoe scotoma from geographic atrophy involving the macular region showed a loss of stimulation to the cortical areas representing the site of the atrophic lesion. Conclusions Cortical retinotopic mapping can be performed successfully in patients with central scotomas from macular disease. This study can serve as a basis for the future investigation of cortical plasticity in visual cortex.

Atrophic macular degeneration mutations in ELOVL4 result in the intracellular misrouting of the protein

Elongation of very long chain fatty acids 4 ( ELOVL4) is a novel member of the ELO family of genes that are involved in fatty acid metabolism. ELOVL4 encodes a putative transmembrane protein of 314 amino acids that carries a possible endoplasmic reticulum (ER) retention/retrieval signal (KXKXX) at the C-terminus. Two distinct mutations, a 5-bp deletion and a complex mutation from the same region in exon 6 of this gene, have been reported so far and are associated with autosomal dominant atrophic macular degeneration (adMD/STGD3). Both of these deletions could result in C-terminal truncation and loss of the ER retention signal in the mutant protein. We expressed the wild-type and mutant proteins in COS-7 and CHO cells to study the intracellular distribution of ELOVL4 and to identify possible implications of the above mutations in its localization. Immunofluorescence analysis of these proteins along with organelle marker antibodies revealed predominant ER localization for wild-type ELOVL4. Targeted deletion of the dilysine motif at the C-terminus of the protein resulted in the loss of ER localization. Immunoelectron microscopy and immunofluorescence analysis revealed a similar ER localization pattern for the protein in human photoreceptors. These data indicate that ELOVL4 is an ER-resident protein, which supports its suggested function in fatty acid elongation. We also demonstrate that the localization of both mutant proteins was dramatically changed from an ER to a Golgi distribution. Our observations suggest that the consequences of defective protein trafficking could underlie the molecular mechanism associated with degeneration of the macula in the patients with adMD/STGD3.

Relationship between refraction and prevalent as well as incident age-related maculopathy: the Rotterdam Study.

To study the relationship between baseline spherical equivalents (SphE) of refraction and prevalent as well as incident age-related maculopathy (pARM and iARM, respectively). The study was performed as part of the Rotterdam Study, a population-based, prospective cohort study. The SphE (in diopters), measured with autorefraction and subjective optimization, was recorded in 6209 subjects aged 55 years or more. Aphakic or pseudophakic eyes at baseline were excluded. Stereoscopic transparencies of the macular region were graded according to the International Classification and Grading System. ARM was defined as large soft drusen with pigmentary changes, or indistinct drusen, or atrophic or neovascular age-related macular degeneration (AMD). For the prevalence analyses, ARM was classified into no, p(early)ARM, or pAMD, and in each subject the eye with the most advanced ARM and the corresponding refraction was selected. After a mean 5.2 years of follow-up, 4935 subjects had complete data for these incidence analyses. In each subject, the eye with iARM was selected. The age- and gender-adjusted odds ratio (OR) of pARM (n = 536) for every diopter of progress toward hyperopia was 1.09 (95% confidence interval [CI]1.04-1.13). For p(early)ARM (n = 440) the OR was 1.09 (1.04-1.14) and for pAMD (n = 96) the OR was 1.09 (1.00-1.19). Baseline refraction was significantly associated with increased risk of iARM (n = 497). For each diopter of progress toward hyperopia the OR was 1.05 (95% CI 1.01-1.10). Additional adjustments for smoking, atherosclerosis, and blood pressure did not alter the relationship. These population-based incidence data confirm results from prevalence and case-control studies that there is an association between hyperopia and ARM.

X-Linked Recessive Atrophic Macular Degeneration from RPGR Mutation

We mapped a new X-linked recessive atrophic macular degeneration locus to Xp21.1–p11.4 and show allelic involvement of the gene RPGR, which normally causes severe peripheral retinal degeneration leading to global blindness. Ten affected males whom we examined had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration, emphasizing the dissociation of atrophic macular degeneration from generalized cone degenerations, including X-linked cone dystrophy (COD1). The RPGR gene nonsense mutation G→T at open reading frame (ORF)15+1164 cosegregated with the disease and may create a donor splice site. Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies.

A new locus for dominant drusen and macular degeneration maps to chromosome 6q14

PURPOSE: To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. METHODS: Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. RESULTS: The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. CONCLUSIONS: In a family with autosomal dominant drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration.

Clinical spectrum of chromosome 6–linked autosomal dominant drusen and macular degeneration

PURPOSE: To describe the clinical phenotype and the intrafamilial variation in retinal findings in a North American family with an autosomal dominant drusen disorder that maps to chromosome 6q14. METHODS: Ophthalmic examinations were carried out on participating family members. Fundus photographs were obtained whenever possible. Electroretinography was performed on the proband and her father. Blood was drawn for DNA analysis. RESULTS: Twelve family members had drusen and/or atrophic macular degeneration. The disease in asymptomatic young adults is characterized by fine drusen that are most conspicuous in the macula. The proband presented at 3 years of age with atrophic maculopathy and drusen. Her cousin was found to have atrophic macular lesions and drusen in the first year of life. Two older affected individuals have reduced vision from cicatricial and atrophic macular changes. The gene for the disease was mapped to chromosome 6q14 and appears to be adjacent to but distinct from the locus for North Carolina macular dystrophy. CONCLUSIONS: There is extreme variability in the clinical expression of this dominant form of drusen and macular degeneration. Most young adults have fine macular drusen and good vision. Affected infants and children may have congenital atrophic maculopathy and drusen. There is historical evidence of progression of the disease in late adulthood with moderate visual loss.

Genetic risk of age-related maculopathy. Population-based familial aggregation study.

To investigate to what extent age-related maculopathy (ARM) is genetically determined. Familial aggregation study based on probands derived from the population-based Rotterdam Study. First-degree relatives of 87 patients with late ARM, i.e., atrophic or neovascular macular degeneration, were compared with first-degree relatives of 135 control subjects without ARM. Presence and stage of ARM as diagnosed on fundus transparencies, odds ratio, lifetime risk, risk ratio, and population-attributable risk. Independent of other risk factors, the prevalence of early (odds ratio = 4.8, 95% confidence interval [CI] = 1.8-12.2) and late (odds ratio = 19.8, 95% CI = 3.1-126.0) ARM was significantly higher in relatives of patients with late ARM. The lifetime risk estimate of late ARM was 50% (95% CI = 26%-73%) for relatives of patients vs 12% (95% CI = 2%-16%) for relatives of controls (P < .001), yielding a risk ratio of 4.2 (95% CI = 2.6-6.8). Relatives of patients expressed the various features of ARM at a younger age. The population-attributable risk related to genetic factors was 23%. First-degree relatives of patients with late ARM developed ARM at an increased rate at a relatively young age. Our findings indicate that approximately one fourth of all late ARM is genetically determined and suggest that genetic susceptibility may play an important role in determining the onset of disease.

A practice-based survey of familial age-related maculopathy

PURPOSE : We evaluated the efficacy of a practice-based survey of age-related maculopathy (ARM) to identify potential families for molecular genetic studies. Demographic and ophthalmic features of the eligible study population were compared with responders and with individuals who reported a positive family history of ARM. METHODS : Individuals seen within a three-year period in a comprehensive ophthalmic practice were identified through billing codes. Clinical records were reviewed, coded, and merged with questionnaire responses. Patient identifiers were removed prior to analyses. RESULTS : There were no significant differences between the respondents and the eligible cohort with respect to gender, age, or type of macular degeneration. Comparable percentages of younger and older individuals with ARM reported positive family histories. The distribution of atrophic macular degeneration, choroidal neovascular membranes, and milder forms of the disease among the individuals reporting positive family histories corresponded to the distribution of the entire eligible cohort of patients. CONCLUSIONS : This recruitment strategy for ARM families is cost-effective and confirmed a high prevalence of familial ARM. The respondents are representative of the general ARM population. This approach is applicable for other ophthalmic genetic conditions.

Vision testing in atrophic macular degeneration.

To determine the correlation between a group of vision tests in atrophic macular degeneration (AMD) in an office setting. Patients with documented vision loss from atrophic macular degeneration in one eye were invited to attend an eye clinic every three months for a series of six vision tests for their good eye followed by fundus photography. Modified contrast sensitivity, blue/yellow anomaloscopy, flicker fusion frequency, Amsler grid, and photostress recovery time were correlated with Snellen acuity using the Pearson correlation coefficient. The regression of the Snellen acuity on sex, age and the presence of disciform macular degeneration in the other eye was obtained using a general linear model. The correlation with Snellen acuity result was low for all tests. It was highest for Amsler grid abnormality (r = -0.33345) and blue/yellow anomaloscopy matching range (r = -0.20742), where r denotes the correlation coefficient. Patient age was strongly correlated with Snellen results (P = 0.0001), but it was not significantly related to sex (P = 0.1187) or the presence of disciform macular degeneration in the other eye (P = 0.9989). The photostress recovery time showed enormous inter-visit variations and poor correlation with Snellen acuity (P = 0.0526). The course of AMD is routinely assessed by Snellen acuity and any of several additional tests. When employing a test battery in an office setting, a clinician needs to know the relative utility and correlation between the tests at his disposal. Of the tests used in this study, the Amsler grid was the most useful addition to the Snellen acuity at all stages of atrophic macular degeneration, and blue/yellow anomaloscopy was useful only in mild macular degeneration where Snellen acuity was 6/12 or better.

The Prevalence of Age-related Maculopathy in the Rotterdam Study

To determine the prevalence of age-related maculopathy in an elderly population in The Netherlands. Fundus photographs of 6251 participants of the Rotterdam Study, a single-center prospective follow-up study in persons 55 to 98 years of age, were reviewed for the presence of drusen, pigmentary abnormalities, and atrophic or neovascular age-related macular degeneration. The prevalence of at least one drusen of 63 microns or larger increased from 40.8% in persons 55 to 64 years of age to 52.6% in those 85 years of age or older. Similarly, the prevalence of the following abnormalities increased significantly in these age categories: drusen of 125 microns or larger from 4.8% to 17.5%, retinal pigment epithelial hypopigmentations from 3.5% to 9.0%, and increased retinal pigment from 3.7% to 15.3%. Atrophic or neovascular age-related macular degeneration was present in 1.7% of the total population. Atrophic age-related macular degeneration increased from 0.1% in persons 55 to 64 years of age to 3.7% in those 85 years of age or older. Neovascular age-related macular degeneration increased from 0.1% to 7.4% in these age groups. No sex differences were observed for these lesions. The prevalence of atrophic or neovascular age-related macular degeneration is 1.7%. In those 55 years of age or older, the prevalence increases strongly with age and it is similar in men and women. Neovascular age-related macular degeneration was twice as common as atrophic age-related macular degeneration. These findings suggest that age-related maculopathy may be less common in this European population than in similar populations in the United States.

Natural course in fellow eyes of patients with unilateral age‐related exudative maculopathy

A prospective fluorescein angiographic study of 45 patients with unilateral age-related exudative maculopathy revealed at the 4-year follow-up that 14 (31%) had developed neovascular membranes in the fellow eyes. Age, drusen size and confluence, as well as pigmentary changes of these 14 were compared with the corresponding characteristics of the 31 eyes that remained non-exudative (atrophic). No significant differences were found. Among the 14 eyes that developed exudative maculopathy, visual acuity (Snellen) deteriorated 3-4 steps in 6 eyes (43%), 5-6 steps in 4 eyes (28.5%), and 7-8 steps or more in 4 eyes (28.5%). Among the 31 eyes that remained non-exudative, visual acuity was unchanged in 20 eyes (64%), deteriorated 1-2 steps in 7 eyes (23%), 3-4 steps in 3 eyes (10%), and 5-6 steps in 1 eye (3%). Social blindness (6/60 or less in the better eye) was found among 79% of the patients who had developed exudative maculopathy, whereas the figure was 19% among patients who still had atrophic macular degeneration.

Risk factor analysis for atrophic and exudative age-related macular degeneration. An epidemiological study of 1000 aged individuals.

The relationship between age-related macular degeneration and cardiovascular risk factors and certain life-style factors, collected in the Copenhagen City Heart Study (1981-83), was studied by multiple logistic regression analysis. The ophthalmological study sample comprised 1000 randomly selected persons aged 60 to 80 years. Separate analyses were made for the atrophic and the exudative forms of age-related macular degeneration. Among all the possible risk factors analysed, only three factors were significantly associated with macular degeneration. Age was associated with both atrophic and exudative macular degeneration (P less than 0.01). Among smokers who inhaled, the risk of atrophic maculopathy was 2.5 times higher than among non-smokers (P less than 0.01), whereas the use of hypnotics increased the risk of exudative maculopathy by 3.4 times (P less than 0.01).

Foveal Drusen Resorption One Year after Perifoveal Laser Photocoagulation

Abstract“Soft” drusen maculopathy is an important precursor of exudative and atrophic macular degeneration. Resorption of soft drusen at the macula in response to laser photocoagulation has been demonstrated previously. The case described in this article is unique because it documents progression of soft drusen maculopathy prior to laser and shows a better visual and morphologic result than in previous studies. In this case, perifoveal laser photocoagulation caused the complete resorption not only of the treated drusen but also the untreated subfoveal and perifoveal drusen. Foveal morphology was restored, visual acuity improved from 20/40 to 20/20, and metamorphopsia diminished. This uniquely favorable response to photocoagulation may result from the treatment of the drusen maculopathy before atrophic, exudative, or neovascular complications. This result shows the need for establishing indications for this treatment through a prospective clinical study and for investigating its mechanism of action.

Primary success with low vision aids in age‐related macular degeneration

The benefit obtained from various low vision aids (LVAs) was studied in 65 consecutive patients with atrophic (70.3%) or disciform (29.7%) age-related macular degeneration (ARMD). 13.8% were able to read newsprint with age-related reading correction under proper lighting conditions. The primary success achieved with LVAs was good, 91.4% of patients being able to read newsprint. In most cases a simple magnifier (52.3%), high-powered reading glasses (10.8%) or Fonda's glasses (12.8%) were sufficient. The magnification preferred was 5x or less in 25.6% and greater than 5x to 9x in 48.8%. Patients with disciform degeneration required higher magnification than those with atrophic degeneration. It is concluded that most patients with ARMD found low vision aids useful for reading purposes and that a simple optical device was sufficient to achieve reading vision.