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PubMed1998

Visual acuity and visual field impairment in Usher syndrome.

OBJECTIVE: To determine the extent of visual acuity and visual field impairment in patients with types 1 and 2 Usher syndrome. METHODS: The records of 53 patients with type 1 and 120 patients with type 2 Usher syndrome were reviewed for visual acuity and visual field area at their most recent visit. Visual field areas were determined by planimetry of the II4e and V4e isopters obtained with a Goldmann perimeter. Both ordinary and logistic regression models were used to evaluate differences in visual acuity and visual field impairment between patients with type 1 and type 2 Usher syndrome. RESULTS: The difference in visual acuity of the better eye between patients with type 1 and type 2 varied by patient age (P=.01, based on a multiple regression model). The maximum difference in visual acuity between the 2 groups occurred during the third and fourth decades of life (with the type 1 patients being more impaired), while more similar acuities were seen in both younger and older patients. Fifty-one percent (n=27) of the type 1 patients had a visual acuity of 20/40 or better in at least 1 eye compared with 72% (n=87) of the type 2 patients (age-adjusted odds ratio, 3.9). Visual field area to both the II4e (P=.001) and V4e (P<.001) targets was more impaired in the better eye of type 1 patients than type 2 patients. A concentric central visual field greater than 20 degrees in at least 1 eye was present in 20 (59%) of the available 34 visual fields of type 1 patients compared with 70 (67%) of the available 104 visual fields of type 2 patients (age-adjusted odds ratio, 2.9) with the V4e target and in 6 (21%) of the available 29 visual fields of type 1 patients compared with 36 (38%) of the available 94 visual fields of type 2 patients (age-adjusted odds ratio, 4.9) with the II4e target. The fraction of patients who had a visual acuity of 20/40 or better and a concentric central visual field greater than 20 degrees to the II4e target in at least 1 eye was 17% (n=5) in the type 1 patients and 35% (n=33) in the type 2 patients (age-adjusted odds ratio, 3.9). CONCLUSIONS: Visual acuity and visual field area were more impaired in patients with type 1 than type 2 Usher syndrome. Of note, 27 of 53 type 1 (51%) and 87 of 120 type 2 (72%) patients had a visual acuity of 20/40 or better in at least 1 eye. These data are useful for overall counseling of patients with Usher syndrome.

Adult↗
PubMed1999

Representation of the visual field in the human occipital cortex: a magnetic resonance imaging and perimetric correlation.

OBJECTIVES: To evaluate the retinotopic map of the human occipital cortex by correlating magnetic resonance imaging (MRI) findings with visual field defects in patients with occipital lobe infarcts and to assess the compatibility between our cliniconeuroimaging findings and the location of lesions predicted by the classic Holmes map and a revised map. METHODS: Magnetic resonance images were obtained in 14 patients with occipital lobe infarcts. Visual field analysis was performed with tangent screen, the Goldmann perimeter, and the Humphrey Field Analyzer. Based on the pattern of visual field deficit, the location of the lesion in the mesial occipital lobe in each patient was predicted using the Holmes map and other retinotopic maps of the occipital cortex. The predicted location of the lesion was then compared with its actual location shown on MRI to assess the compatibility between our data and the other maps. These maps determine retinotopic correlates of the medial occipital lobe, but they cannot establish correlates of the striate cortex (V1). The medial occipital representation of central vision was evaluated by regression analysis. RESULTS: The MRI correlations in this study confirmed gross estimates of the retinotopic organization of the occipital cortex. However, our findings did not correlate exactly with the Holmes map. We determined that the central 15 degrees of vision occupies 37% of the total surface area of the human medial occipital lobe. Based on our data, a refined retinotopic map is presented. CONCLUSIONS: The resolution of conventional MRI testifies to its considerable value in localizing occipital lobe lesions. Our findings support, and refine, the Holmes map of the human occipital cortex.

Adolescent↗
PubMed1999

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

OBJECTIVE: To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. PATIENTS: Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. METHODS: Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. RESULTS: Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. CONCLUSIONS: A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. CLINICAL RELEVANCE: The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.

ATP-Binding Cassette Transporters↗
PubMed1999

Methodological variations in estimating apparent progressive visual field loss in clinical trials of glaucoma treatment.

OBJECTIVES: To compare methods to estimate the incidence of visual field progression used by 3 large randomized trials of glaucoma treatment by applying these methods to a common data set of annually obtained visual field measurements of patients with glaucoma followed up for an average of 6 years. METHODS: The methods used by the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the Early Manifest Glaucoma Treatment study (EMGT) were applied to 67 eyes of 56 patients with glaucoma enrolled in a 10-year natural history study of glaucoma using Program 30-2 of the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, Calif). The incidence of apparent visual field progression was estimated for each method. Extent of agreement between the methods was calculated, and time to apparent progression was compared. RESULTS: The proportion of patients progressing was 11%, 22%, and 23% with AGIS, CIGTS, and EMGT methods, respectively. Clinical assessment identified 23% of patients who progressed, but only half of these were also identified by CIGTS or EMGT methods. The CIGTS and the EMGT had comparable incidence rates, but only half of those identified by 1 method were also identified by the other. CONCLUSIONS: The EMGT and CIGTS methods produced rates of apparent progression that were twice those of the AGIS method. Although EMGT, CIGTS, and clinical assessment rates were comparable, they did not identify the same patients as having had field progression.

Disease Progression↗
PubMed2000

Transplantation of autologous iris pigment epithelium after removal of choroidal neovascular membranes.

BACKGROUND: Transplantation of autologous iris pigment epithelium (IPE) into the subretinal space has been suggested as one approach for the treatment of age-related macular degeneration, as well as for other conditions in which loss of retinal pigment epithelium (RPE) occurs. Surgical removal of choroidal neovascular membranes is associated with traumatic loss of the RPE cell layer, disruption of the integrity of the photoreceptor-RPE complex, and limited visual outcome. OBJECTIVE: To examine whether IPE cells can substitute for RPE cells to be transplanted to the subretinal space of patients with either RPE degenerative disease or traumatic loss of the RPE cell layer after subretinal surgery. METHODS: Autologous IPE cells were transplanted to the subretinal space in 20 consecutive patients undergoing removal of subretinal fibrovascular membranes using pars plana vitrectomy. Autologous IPE cells were harvested by iridectomy, isolated, and transplanted directly to the subretinal spaces. Transplants were evaluated for 6 to 11 months by funduscopy, fluorescein angiography, and scanning laser ophthalmoscopic (SLO) microperimetry. RESULTS: For the entire follow-up period, no evidence of any immunologic response was observed. Revisional surgery was necessary in 3 patients because of complications (rhegmatogenous retinal detachment [n = 1]; proliferative vitreoretinopathy [n = 1]; and macular pucker [n = 1]); 1 patient did not receive IPE cells. Five of 19 phakic eyes underwent cataract surgery; in 1 case this was combined with the vitrectomy. Five patients showed improved visual acuity of 3 to 4 lines, 13 patients had stable visual acuity (+/-2 lines), and 2 patients had reduced visual acuity of 6 lines. CONCLUSIONS: In this pilot study, the transplantation of autologous IPE cells was done as an addition to conventional surgical excision of choroidal neovascular membranes. Transplanted cells were well tolerated in the subretinal space and did not adversely affect the function of the photoreceptors, since improvement or stable visual acuity was observed in 18 patients after IPE transplantation. These results suggest that autologous IPE cells may be used as a substitute for autologous RPE cells to transplant to the subretinal space to treat age-related macular degeneration.

Adult↗
PubMed2000

Papilledema and obstructive sleep apnea syndrome.

OBJECTIVES: To characterize the pathogenesis and clinical features of optic disc edema associated with obstructive sleep apnea syndrome (SAS). METHODS: A series of 4 patients with SAS and papilledema (PE) underwent complete neuro-ophthalmologic evaluation and lumbar puncture. In 1 patient, continuous 24-hour intracranial pressure (ICP) monitoring was also performed. RESULTS: All 4 patients had bilateral PE that was asymmetric in 2. Three patients had optic nerve dysfunction, asymmetric in 1, unilateral in 2. Daytime cerebrospinal fluid pressure measurements were within normal range. Nocturnal monitoring performed in one patient, however, demonstrated repeated episodes of marked ICP elevation associated with apnea and arterial oxygen desaturation. CONCLUSIONS: We propose that PE in SAS is due to episodic nocturnal hypoxemia and hypercarbia resulting in increased ICP secondary to cerebral vasodilation. In these individuals, intermittent ICP elevation is sufficient to cause persistent disc edema. These patients may be at increased risk for developing visual loss secondary to PE compared with patients with obesity-related pseudotumor cerebri because of associated hypoxemia. The diagnosis of SAS PE may not be appreciated because daytime cerebrospinal fluid pressure measurements are normal and because patients tend to present with visual loss rather than with symptoms of increased ICP.

Acetazolamide↗
PubMed2000

Scanning laser ophthalmoscope correlations with biomicroscopic findings and foveal function after macular hole closure.

OBJECTIVE: To investigate the relation between foveal findings and visual function in eyes with a resolved idiopathic macular hole after vitreous surgery. METHODS: We divided 28 eyes with postoperative idiopathic macular hole resolution into 3 groups based on postoperative biomicroscopic foveal findings of complete closure, partial closure, or atrophic closure. To evaluate foveal retinal function, scanning laser ophthalmoscope (SLO) microperimetry was performed preoperatively and 6 months postoperatively. RESULTS: Postoperatively in 18 eyes (64%), the foveal images became normal or almost normal and were classified as having complete closure, 6 eyes (21%) were classified as having partial closure, and 4 eyes (14%) as having atrophic closure. The corresponding visual acuity levels 6 months postoperatively were, respectively, 0.10, 0.35, and 0.64 (P<.01) based on LogMAR analysis. Preoperative SLO microperimetry detected an absolute scotoma at the bottom of all macular holes; postoperatively, the absolute scotoma disappeared in the 18 eyes with complete hole closure, but a relative scotoma was detected in 6 eyes. Of 6 eyes with partial closure, 1 had an absolute scotoma and 5 had a relative scotoma. An absolute scotoma was detected in 4 eyes with atrophic closure. CONCLUSIONS: After macular hole closure, SLO findings correlate both with biomicroscopic findings and foveal function. Better anatomical foveal recovery in eyes after macular hole closure results in better improvement of vision than in eyes in which the foveal anatomical findings are not as good.

Aged↗
PubMed2000

Rate of visual field loss in progressive glaucoma.

OBJECTIVE: To investigate the rate of visual field (VF) loss in progressive glaucoma. SETTING: Outpatient department, nonreferral base. METHODS: A cohort of 34 patients with normal-pressure glaucoma (NPG), 68 patients with primary open-angle glaucoma (POAG), and 125 patients with ocular hypertension (OHT) were followed up for an average of 9 years. Visual fields were obtained annually with automated perimetry. The rate of VF loss as a percentage per year was calculated. RESULTS: Twenty-three eyes with NPG, 31 with POAG, and 10 with OHT showed progression of VF loss. The mean (+/-SD) rates of VF deterioration were 3.7%+/-3.3% per year in NPG, 2.5%+/-1.8% in POAG, and 2.3%+/-1.3% in OHT converting to POAG, and did not differ significantly. No difference in the rate of VF loss was found between eyes with and without optic disc hemorrhages (2.7%+/-2.9% and 3.1%+/-2.1%, respectively). The rate of VF loss was not related to the initial VF status. The rate of VF loss between the superior and inferior hemifields was correlated in patients with NPG (r(s) = 0.67, P = .04). Comparison of visual field loss with linear regression analysis showed significant slopes in only 37.5% of eyes with progression, which had a progression rate of 4.2%+/-3.0%. CONCLUSIONS: The rate of VF loss did not differ between patients with NPG and POAG. The rate of deterioration was related neither to initial VF status nor to the presence of disc hemorrhages. Linear regression is applicable only in a portion of the patients who have progression of VF loss.

Aged↗
PubMed2000

Short-wavelength automated perimetry and standard perimetry in the detection of progressive optic disc cupping.

OBJECTIVE: To compare progression in short-wavelength automated perimetry (SWAP) and white-on-white (standard) perimetry in eyes with progressive glaucomatous changes of the optic disc detected by serial stereophotographs. METHODS: Forty-seven glaucoma patients with at least 2 disc stereophotographs more than 2 years apart, along with standard perimetry and SWAP examinations within 6 months of each disc photo of the same eye, were included in the study. The mean follow-up time was 4.1 years (range, 2.0-8.9 years). Baseline and follow-up stereophotographs were then graded and compared for the presence of progression. Progression in standard perimetry and SWAP, using the Advanced Glaucoma Intervention Study scoring system and a clinical scoring system, was compared between eyes with progressive change on stereophotographs and those without. RESULTS: Twenty-two of 47 eyes showed progressive change by stereophotographs. There was a statistically significant difference in the mean change in Advanced Glaucoma Intervention Study scores for both standard perimetry (P<.004) and SWAP (P<.001) between the progressed and nonprogressed groups. The sensitivity, specificity, and area under the receiver operator characteristic curve were higher using SWAP than standard perimetry when evaluated by either algorithm. This was statistically significant only in the area under the receiver operator characteristic curve for the Advanced Glaucoma Intervention Study scoring system (P =.04). CONCLUSIONS: Short-wavelength automated perimetry identified more patients than standard perimetry as having progressive glaucomatous changes of the optic disc. Compared with standard perimetry, SWAP may improve the detection of progressive glaucoma. Arch Ophthalmol. 2000;118:1231-1236

Aged↗
PubMed2000

Description of a new mutation in rhodopsin, Pro23Ala, and comparison with electroretinographic and clinical characteristics of the Pro23His mutation.

OBJECTIVES: To report the clinical characteristics of a family with autosomal dominant retinitis pigmentosa caused by a proline-to-alanine mutation at codon 23 (Pro23Ala) of the rhodopsin gene and to compare this phenotype with that associated with the more common proline-to-histidine mutation at codon 23 (Pro23His). METHODS: We examined 6 patients within a single pedigree. The electroretinograms (ERGs) of 35 patients with known Pro23His mutations and of 22 healthy individuals were reviewed. Scotopic dim flash-response amplitudes, maximum combined-response amplitudes, and photopic-response amplitudes from the ERGs of these patients were plotted against age. The ERG indices of 5 individuals in the Pro23Ala family were compared with those of the patients with Pro23His mutations and of healthy individuals. Multiple linear regression was performed to evaluate the effect of age and mutation type on amplitudes. Mutation detection was performed using single-strand conformation polymorphism analysis, followed by automated DNA sequencing. RESULTS: Patients with the Pro23Ala mutation have a clinical phenotype characterized by onset of symptoms in the second to fourth decades of life, loss of superior visual field with relatively well-preserved inferior fields, and mild nyctalopia. Comparison with patients with the Pro23His mutation demonstrates statistically significant differences (P<.001) in responses to dim flash, maximum combined, and photopic responses between patients with these mutations after controlling for the effects of age. Patients with Pro23Ala mutations were less affected by ERG criteria than patients with Pro23His mutations. Patients with Pro23Ala mutations also differed significantly from healthy patients in all ERG indices examined (P<.001), after controlling for age. CONCLUSION: We describe a rare mutation in codon 23 of rhodopsin causing autosomal dominant retinitis pigmentosa. The retinal dystrophy associated with the Pro23Ala mutation is characteristically mild in presentation and course, with greater preservation of ERG amplitudes than the more prevalent Pro23His mutation. Arch Ophthalmol. 2000;118:1269-1276

Adolescent↗
PubMed2001

Assessment of visual function in patients with gyrate atrophy who are considered candidates for gene replacement.

OBJECTIVE: To assess the course of change of visual function outcome variables in 5 patients with gyrate atrophy before a gene replacement therapy clinical trial. METHODS: The outcome variables selected were visual field sensitivity and electroretinogram amplitude. The course of change of these outcome variables was determined by calculation of their half-lives. RESULTS: In the 4 to 6 years during which each patient was followed up for this study, median visual field half-lives were 17.0 years (static perimetry) and 11.4 years (kinetic perimetry). Median electroretinogram half-lives were 16.0 years (maximal response) and 10.7 years (flicker response). CONCLUSIONS: The course of the decline of visual function outcome variables is frequently slow. Thus, a long-term clinical trial would be required to assess the efficacy of the intervention in the preservation of visual function.

Adult↗
PubMed2002

Visual field defects and multifocal visual evoked potentials: evidence of a linear relationship.

OBJECTIVE: To determine the relationship between spatially localized multifocal visual evoked potentials (mfVEPs) and Humphrey visual fields (HVFs) in patients with unilateral field defects. METHODS: Humphrey visual fields and mfVEPs were obtained from 20 patients with unilateral field losses due to either ischemic optic neuropathy or glaucoma. Monocular mfVEPs were obtained for each eye. The amplitude of the mfVEP responses was calculated using root-mean-square and signal-noise ratio measures. Estimates of the HVF loss in the same regions of the field used for the mfVEP were obtained by interpolating the 24-2 HVF data. RESULTS: Monocular mfVEP amplitude decreased with HVF loss, although small mfVEP signals were not uniquely associated with poor fields. On average, the monocular mfVEP was indistinguishable from noise for field losses between -5 and -10 dB, and good monocular mfVEP amplitudes were never associated with extensive visual field loss. The interocular ratio of the mfVEP amplitudes correlated well with the difference between the HVF values of the 2 eyes, and this correlation improved with increased signal-noise ratio. CONCLUSIONS: The monocular and interocular results were consistent with a linear relationship between the amplitude of the signal portion of the mfVEP response and linear HVF loss. One way to produce this relationship would be if both the signal in the mfVEP and linear HVF loss were linearly related to the percentage of local ganglion cells lost. The clinical limitations of the mfVEP technique can be understood by taking the signal-noise ratio, and the linear model proposed herein, into consideration.

Adult↗
PubMed2002

Macular translocation with 360 degrees retinotomy for exudative age-related macular degeneration.

BACKGROUND: Macular rotation surgery comprises surgical extraction of choroidal neovascular membranes in age-related macular degeneration (AMD) and translocation of the foveal neural retina over adjacent retinal pigment epithelium. OBJECTIVE: To determine whether macular translocation with 360 degrees retinotomy can stabilize and/or improve visual acuity in patients with subfoveal choroidal neovascularization (CNV) secondary to AMD. DESIGN: This study consisted of a standardized surgical procedure on a series of 90 consecutive patients and follow-up examinations at fixed intervals for 12 months. PARTICIPANTS: All patients in this study had experienced recent visual loss resulting from subfoveal CNV caused by AMD. Twenty-six patients had major macular subretinal hemorrhage, 39 patients had occult subfoveal CNV, and 25 patients had classic subfoveal CNV. METHODS: Macular translocation surgery was performed between 1997 and 1999. The patients were examined preoperatively and at 3, 6, and 12 months postoperatively, including visual acuity, microperimetry, angiography, and orthoptic assessment. RESULTS: Visual acuity increased by 15 or more letters in 24 patients, remained stable in 37 patients, and deteriorated by 15 or more letters in 29 patients at 12 months postoperatively. A secondary procedure was necessary in 17 patients because of severe complications; proliferative vitreoretinopathy was observed in 17 eyes, macular pucker in 5 eyes, and macular hole in 1 patient. CONCLUSION: Macular translocation is a technically demanding surgical procedure. Although the procedure has a high rate of surgical and postoperative complications, the functional and anatomical results appear to be promising for selected patients with subfoveal CNV secondary to AMD.

Aged↗
PubMed2002

The structure-function relationship in eyes with glaucomatous visual field loss that crosses the horizontal meridian.

OBJECTIVE: To evaluate the relationship between visual field loss and glaucomatous optic discs in eyes in which field loss spreads across the horizontal meridian. SUBJECTS AND METHODS: Ninety-six patients with glaucoma (9 advanced, 60 moderate, and 27 early) with 2 successive abnormal fields were included. Standard achromatic automated perimetry defects were identified with a nerve fiber bundle map to identify abnormal sectors. Crossover was present if the superior and inferior sectors at the horizontal meridian (nasal, central, or temporal) were both abnormal. Optic disc damage was assessed by masked grading of simultaneous stereophotographs. RESULTS: Only 30% (29) of glaucomatous eyes showed crossover, and only 2 of those eyes had early loss. The most frequent pattern of visual field loss (41% of eyes) was single hemifield damage with defects in contiguous sectors. Regardless of the pattern or severity of visual loss, most eyes (66 [69%] of 96) had both superior and inferior optic disc damage. CONCLUSIONS: Early glaucomatous visual field loss rarely crosses the horizontal meridian, but defects in both hemifields at the horizontal meridian are more common in more advanced field loss. In 26 (90%) of 29 eyes with crossover, it could be explained by changes at the optic nerve head.

Adult↗
PubMed2003

Detection of early visual field loss in glaucoma using frequency-doubling perimetry and short-wavelength automated perimetry.

OBJECTIVE: To investigate whether frequency-doubling perimetry (FDP) predicts future visual field loss with achromatic automated perimetry (AAP), just as it may be predicted with short-wavelength automated perimetry (SWAP). METHODS: We recruited 62 patients selectively from an urban glaucoma practice. At the commencement of the study, each patient had ocular hypertension with normal visual fields on AAP. Baseline SWAP and FDP were performed to determine whether underlying earlier visual field loss was present. Patients were then followed up prospectively for 3 years with annual AAP, SWAP, and FDP. Main Outcome Measure The development of visual field loss on AAP. RESULTS: Nine subjects had abnormal SWAP findings and 10 had abnormal FDP findings. At the conclusion of the study, field loss on AAP developed in 5, all of whom had preexisting abnormal SWAP and FDP results. No AAP visual field loss developed in patients with a normal SWAP or FDP. The rate of development of visual field loss on AAP was therefore significantly greater for those with abnormal SWAP (chi21 = 40.83; P<.001) and abnormal FDP findings (chi21 = 32.76; P<.001) than for those with normal SWAP and FDP findings. CONCLUSION: In the same way that SWAP may predict AAP visual field loss, FDP may also detect field loss earlier than AAP.

Female↗