Purpose
Mutations in the RLBP1 gene encoding the cellular retinaldehyde‐binding protein (CRALBP) cause autosomal recessive progressive retinopathy, such as retinitis punctata albescens (RPA), ...Bothnia‐type dystrophy (BD), Newfoundland rod‐cone dystrophy (NFRCD), retinitis pigmentosa (RP) and fundus albipunctatus (FA). We present the clinical heterogeneity and genetic findings of seven patients from five families with RLBP1 mutations, including three novel mutations.
Methods
Seven patients underwent complete ophthalmological examination including psychophysical tests (visual acuity, colour vision, visual field, dark adaptation) and electrophysiology (Ganzfeld and multifocal ERG). Additionally, fundus photography, autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) recordings were performed. Genomic DNA was analysed by high‐throughput sequencing for all RP‐related genes in a diagnostic set‐up.
Results
The patients presented with variable phenotypes, including RPA, BD, RP and a mild form of NFRCD. No detectable or severely depressed responses in electrophysiological examinations were seen in all cases. Visual field constriction was variable among individuals. Severely reduced visual acuity was only observed in the patient presenting with BD. The other patients retained mild to moderate reduction of visual function. Despite the morphological differences, central retinal thinning – as a common feature – could be observed.
Conclusions
The fact that different mutations in RLBP1 are correlated with quite different morphological and functional characteristics outlines the complexity of the protein. Identifying new mutations and comparing the different phenotypes may help to better understand the function of the protein and the consequences in pathological changes that involve RPE and choroid.
Achromatopsia (ACHM) is a rare autosomal recessive inherited retinal disorder with an incidence of approximately 1 in 30,000. It presents at birth or early infancy and is typically characterized by ...reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. The symptoms arise from isolated cone dysfunction, which can be caused by mutations in the crucial components of the cone phototransduction cascade. Although ACHM is considered a functionally nonprogressive disease affecting only the cone system, recent studies have described progressive age-dependent changes in retinal architecture. Currently, no specific therapy is available for ACHM; however, gene replacement therapy performed on animal models for three ACHM genes has shown promising results. Accurate genetic and clinical diagnosis of patients may therefore enhance and enable therapeutic intervention in the near future. This short review summarizes the genetic background, pathophysiology, clinical findings, diagnostics, and therapeutic perspectives in ACHM.
Mutations in the retinitis pigmentosa-1-like-1 (RP1L1) gene are the major cause of autosomal dominant occult macular dystrophy (OCMD), while recessive mutations have been linked to autosomal ...recessive retinitis pigmentosa (arRP). We present the clinical phenotype of a large German OCMD cohort, as well as four RP patients.
A total of 42 OCMD patients (27 families) and 4 arRP patients (3 families) with genetically confirmed mutations in RP1L1 were included. Genomic DNA was analyzed by targeted analysis of the c.133C>T;p.R45W mutation for all RP or macular dystrophy-related genes. All patients underwent ophthalmologic examination including psychophysical tests, electrophysiology, fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT). Follow-up time was up to 12 years.
In 25 OCMD index patients genomic testing revealed the heterozygous mutation c.133C>T;p.R45W in RP1L1; one patient was homozygous for the mutation. Two OCMD patients displayed the variants c.3599G>A;p.G1200D and c.2849G>A;p.R950H, respectively, in a heterozygous state. All OCMD patients showed characteristic clinical findings and typical microstructural photoreceptor changes. Two arRP patients displayed the novel homozygous mutations c.3022C>T;p.Q1008* and c.1107G>A;p.W369*, respectively, while two RP-siblings carried the two heterozygous mutations c.455G>A;p.R152Q and c.5959C>T;p.Q1987*, the first also being novel. All arRP cases were mild with disease onset ≈30 years and preserved ERG-responses.
OCMD phenotype showed consistent clinical findings including classical microstructural changes on SD-OCT. An important hallmark of RP1L1-related OCMD is the dominant family history with reduced penetrance. Furthermore, novel mutations in association with arRP were identified, outlining the complexity of the protein.
The purpose of this study was to clinically characterize patients with CNGA3-linked achromatopsia (CNGA3-ACHM) in preparation of a gene therapy trial.
Thirty-six patients (age 7-56 years) with ...complete (cACHM) or incomplete (iACHM) CNGA3-ACHM were examined, including detailed psychophysical tests, extended electrophysiology, and assessment of morphology by fundus autofluorescence and spectral-domain optical coherence tomography (SD-OCT).
Mean best-corrected visual acuity was 0.78 ± 0.14 logMAR. Color vision tests were consistent with a rod-dominated function in every cACHM patient. Microperimetry indicated an overall lowered retinal sensitivity within 20° of visual field. In electroretinography (ERG), photopic responses were nondetectable in cACHM patients, but residual cone responses were observed in the iACHM patients. Scotopic responses were altered referring to anomalies of photoreceptor and postreceptor signaling, whereas in voltage versus intensity functions, Vmax was significantly below normal values (P < 0.05). In contrast, slope (n) and semisaturation intensity (K) were found to be within normal limits. Spectral-domain OCT examination showed no specific changes in 14.7%, disruption of the ellipsoid zone (EZ) at the fovea in 38.2%, absent EZ in 17.7%, a hyporeflective zone in 20.5%, and outer retinal atrophy in 8.9% of all cases and foveal hypoplasia in 29 patients (85%). No correlation of retinal morphology with visual function or with a specific genotype was found. The severity of morphologic and functional changes lacked a robust association with age.
Our extended investigations prove that even among such a genetically homogenous group of patients, no specific correlations regarding function and morphology severity and age can be observed. Therefore, the therapeutic window seems to be wider than previously indicated.
Introduction: The aim of this study was to evaluate the relation between choroidal thickness (CT), central retinal thickness (CRT) and best-corrected visual acuity (BCVA) after surgery for idiopathic ...epiretinal membrane (iERM). Methods: Patients with 4 severity stages of iERM, who underwent vitrectomy with membrane- and internal limiting membrane peeling, were included in this prospective study. CRT, CT, and BCVA were assessed at baseline (BSL), 1 week, 1 and 3 months postoperatively. Results: Twenty-one eyes were phakic, 11 eyes pseudophakic at BSL, in 14 cases combined cataract surgery was performed. BCVA was highest in stage 1 and 2, lowest in stage 4 iERM (p < 0.001) and correlated with CRT. After surgery, CRT decreased and BCVA increased significantly (p < 0.05). CT did not show significant differences among stages (p = 0.23). BSL CRT did not differ between phakic and pseudophakic eyes, the least reduction after surgery was detected in patients who underwent combined cataract surgery and vitrectomy. BSL CT was greater in phakic than in pseudophakic eyes (p = 0.033). Postoperative CT decreased in pseudophakic and phakic eyes, but remained higher after combined surgery (p = 0.0048). Conclusion: CT is not related to the severity of iERM. Choroidal changes did not influence the BCVA. Additional cataract surgery seems to cause longer recovery in CT and CRT.
Purpose
Cannabis is a psychotomimetic agent that induces impairment of sensory perception. We present detailed clinical and electrophysiological data of patients with hallucinogen persisting ...perception disorder (HPPD) after marijuana consumption.
Methods
A HPPD patient and four heavy cannabis smokers with no visual disturbances (controls) underwent complete ophthalmological examination including psychophysical tests (visual acuity, color vision, visual field, and dark adaptation) and detailed electrophysiological examinations, including extended Ganzfeld ERG, multifocal ERG, and electrooculography (EOG). Furthermore, electrically evoked phosphene thresholds (EPTs) were measured to further evaluate retinal function.
Results
Ophthalmological and most electrophysiological examinations were within normal limits for the HPPD patient and for all control subjects. Interestingly, EOG results of the HPPD patient showed a slightly reduced fast oscillation ratio, diminished standing potentials of the slow oscillations, and a light peak within normal range resulting in higher Arden ratios. The EPTs of the patient were reduced, in particular for pulses with long durations (50 ms) causing visual sensations even at lowest possible currents of the neurostimulator. The control subjects did not reveal such alterations.
Conclusions
Our findings suggest a direct effect of cannabinoids on the retina and retinal pigment epithelium function, which may be involved in disturbances of the visual function experienced after drug consumption. The observations presented here may contribute to the elucidation of the detailed mechanism. Furthermore, EOG and EPT measurements may be useful tools to demonstrate long-term retinal alterations in cannabis-induced HPPD in patients.
Abstract
Purpose
Mutations in the
RLBP
1
gene encoding the cellular retinaldehyde‐binding protein (
CRALBP
) cause autosomal recessive progressive retinopathy, such as retinitis punctata albescens (
...RPA
), Bothnia‐type dystrophy (
BD
), Newfoundland rod‐cone dystrophy (
NFRCD
), retinitis pigmentosa (
RP
) and fundus albipunctatus (
FA
). We present the clinical heterogeneity and genetic findings of seven patients from five families with
RLBP
1
mutations, including three novel mutations.
Methods
Seven patients underwent complete ophthalmological examination including psychophysical tests (visual acuity, colour vision, visual field, dark adaptation) and electrophysiology (Ganzfeld and multifocal
ERG
). Additionally, fundus photography, autofluorescence (
FAF
) and spectral domain optical coherence tomography (
OCT
) recordings were performed. Genomic
DNA
was analysed by high‐throughput sequencing for all
RP
‐related genes in a diagnostic set‐up.
Results
The patients presented with variable phenotypes, including
RPA
,
BD
,
RP
and a mild form of
NFRCD
. No detectable or severely depressed responses in electrophysiological examinations were seen in all cases. Visual field constriction was variable among individuals. Severely reduced visual acuity was only observed in the patient presenting with
BD
. The other patients retained mild to moderate reduction of visual function. Despite the morphological differences, central retinal thinning – as a common feature – could be observed.
Conclusions
The fact that different mutations in
RLBP
1
are correlated with quite different morphological and functional characteristics outlines the complexity of the protein. Identifying new mutations and comparing the different phenotypes may help to better understand the function of the protein and the consequences in pathological changes that involve
RPE
and choroid.
Purpose To evaluate a new method for measuring corneal diameter in children. Design Prospective, cross-sectional study. Methods With a digital camera set at maximum focal distance, the authors ...photographed 92 children twice, each with a paper ruler taped to his or her forehead. Images were opened on a personal computer and the lower half of each eye was cut out and dragged to the ruler to record corneal diameter. The coefficient of variation was calculated for each eye, and nonlinear regression analysis used to correlate diameters with age. Results Directly after birth, corneal diameter was 9.98 mm, increasing to a plateau of 11.51 mm within the first 24 months of life. The coefficient of variation was 1.3%. Each measurement took no more than a few minutes. Conclusions This method allows very precise, fast, noncontact measurements of corneal diameter in newborn and young children.
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