Comparison of intraocular light scatter in carriers of choroideremia and X-linked retinitis pigmentosa

doi:10.1016/S0161-6420(01)00854-5

Ophthalmology

Volume 109, Issue 1, January 2002, Pages 159-163

https://doi.org/10.1016/S0161-6420(01)00854-5 Get rights and content

Abstract

Objective

To compare the extent of intraocular straylight in carriers of choroideremia (CHM) and X-linked recessive retinitis pigmentosa (XLRP) to clarify further the relationship between photoreceptor cell degeneration and intraocular light scatter in retinal diseases.

Design

Prospective case-control study.

Participants

Six obligate carriers of CHM, 12 obligate carriers of XLRP, and 30 age-similar control subjects with normal vision. The controls had no posterior subcapsular (PSC) lens opacities, and the carriers had minimal or no PSC lens opacities, as assessed by slit-lamp biomicroscopy.

Main outcome measures

Straylight levels were measured using a van den Berg Straylightmeter. Visual acuity and Goldmann visual field area using a II/4e target were assessed for both eyes of each carrier. Electroretinogram (ERG) data were available on four of six carriers of CHM and all carriers of XLRP. The extent of retinal pigment epithelial degenerative changes was evaluated by fundus examination.

Results

All six carriers of CHM had typical fundus abnormalities with normal visual fields. Five of the six carriers of CHM had age-normal levels of intraocular light scatter, and one showed minimally elevated intraocular light scatter. The 12 carriers of XLRP had a spectrum of fundus abnormalities and varying severity of functional impairment as derived from visual field areas and ERG amplitudes. Seven of the 12 carriers of XLRP showed an elevated level of intraocular light scatter in at least one eye. The degree of straylight elevation above the normal mean age value was correlated significantly with both visual field area and amplitude of the maximal-intensity, dark-adapted ERG b-wave.

Conclusions

The carriers of XLRP who had evidence of photoreceptor cell dysfunction (as determined by visual field loss and reduced ERG amplitudes) had increased levels of intraocular straylight, whereas the carriers of CHM, who showed fundus abnormalities alone, in the absence of demonstrable photoreceptor cell dysfunction, had normal or minimally elevated levels. This finding supports the hypothesis that the increased levels of intraocular light scatter observed in some patients with hereditary retinal degenerations result from subclinical changes in the PSC region of the lens as a consequence of photoreceptor cell degeneration.

Section snippets

Materials and methods

Six obligate female carriers of CHM and 12 obligate female carriers of XLRP participated in the study. Carriers who were older than 65 years were excluded from the study to minimize the effect of age-related changes in the ocular media. Carriers with intraocular lenses or with more than a +1 PSC lens opacity9 in either eye were also excluded. In addition, carriers with a best-corrected visual acuity worse than 20/50 in either eye were also excluded, because it was likely that such carriers

Results

The log SLP values for the individual control subjects are shown as the open circles in Figure 1, Figure 2. These data points represent the average of the log SLP values of the two eyes. For the control subjects, the intraocular light scatter increased with age, as expected.13 As in previous studies,1, 2 we used the formulation of IJspeert et al13 to describe the general trend of data for the control subjects. This is shown by the solid curve in Figure 1, Figure 2. The dashed curves in these

Discussion

In this study, the carriers of CHM, who had clinically apparent fundus abnormalities but no evidence of retinal photoreceptor cell functional impairment, as measured by visual fields and the ERG, showed normal or minimally elevated intraocular light scatter. Similarly, as a group, the carriers of XLRP who had minimal or no functional impairment showed normal or minimally elevated intraocular straylight, whereas those carriers with evidence of functional impairment, based on visual field and ERG

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Cited by (18)

Adeno-Associated Virus Serotype 2–hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial
2022, Ophthalmology
To assess the safety of the subretinal delivery of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human choroideremia (CHM)-encoding cDNA in CHM.
Prospective, open-label, nonrandomized, dose-escalation, phase I/II clinical trial.
Fifteen CHM patients (ages 20–57 years at dosing).
Patients received uniocular subfoveal injections of low-dose (up to 5 × 10¹⁰ vector genome [vg] per eye, n = 5) or high-dose (up to 1 × 10¹¹ vg per eye, n = 10) of a recombinant adeno-associated virus serotype 2 (AAV2) vector carrying a human CHM-encoding cDNA (AAV2-hCHM). Patients were evaluated preoperatively and postoperatively for 2 years with ophthalmic examinations, multimodal retinal imaging, and psychophysical testing.
Visual acuity, perimetry (10-2 protocol), spectral-domain OCT (SD-OCT), and short-wavelength fundus autofluorescence (SW-FAF).
We detected no vector-related or systemic toxicities. Visual acuity returned to within 15 letters of baseline in all but 2 patients (1 developed acute foveal thinning, and 1 developed a macular hole); the rest showed no gross changes in foveal structure at 2 years. There were no significant differences between intervention and control eyes in mean light-adapted sensitivity by perimetry or in the lateral extent of retinal pigment epithelium relative preservation by SD-OCT and SW-FAF. Microperimetry showed nonsignificant (< 3 standard deviations of the intervisit variability) gains in sensitivity in some locations and participants in the intervention eye. There were no obvious dose-dependent relationships.
Visual acuity was within 15 letters of baseline after the subfoveal AAV2-hCHM injections in 13 of 15 patients. Acute foveal thinning with unchanged perifoveal function in 1 patient and macular hole in 1 patient suggest foveal vulnerability to the subretinal injections. Longer observation intervals will help establish the significance of the minor differences in sensitivities and rate of disease progression observed between intervention and control eyes.
Re: van Bree et al.: Straylight as an Indicator for Cataract Extraction in Patients with Retinal Dystrophy
2018, Ophthalmology Retina
Natural History of the Central Structural Abnormalities in Choroideremia: A Prospective Cross-Sectional Study
2017, Ophthalmology
Citation Excerpt :
A large body of literature on the disease expression of CHM hemizygotes has accumulated from its original description more than a century ago. Most studies have focused on changes in VA or peripheral visual field extent measured by kinetic perimetry, with a minority addressing disease progression quantitatively with data from psychophysics, detailed retinal imaging, or electrophysiology, a handful longitudinally, most retrospectively.1-14,49-73 A detailed cross-sectional evaluation of the retinal structure in large groups of patients with this disease at various stages constitutes a practical alternative to partially overcome the relative lack of longitudinal information imposed by this slowly progressive, infrequent disease.
To describe in detail the central retinal structure of a large group of patients with choroideremia (CHM).
A prospective, cross-sectional, descriptive study.
Patients (n = 97, age 6–71 years) with CHM and subjects with normal vision (n = 44; ages 10–50 years) were included.
Subjects were examined with spectral-domain optical coherence tomography (SD OCT) and near-infrared reflectance imaging. Visual acuity (VA) was measured during their encounter or obtained from recent ophthalmic examinations. Visual thresholds were measured in a subset of patients (n = 24) with automated static perimetry within the central regions (±15°) examined with SD OCT.
Visual acuity and visual thresholds; total nuclear layer, inner nuclear layer (INL), and outer nuclear layer (ONL) thicknesses; and horizontal extent of the ONL and the photoreceptor outer segment (POS) interdigitation zone (IZ).
Earliest abnormalities in regions with normally appearing retinal pigment epithelium (RPE) were the loss of the POS and ellipsoid zone associated with rod dysfunction. Transition zones (TZs) from relatively preserved retina to severe ONL thinning and inner retinal thickening moved centripetally with age. Most patients (88%) retained VAs better than 20/40 until their fifth decade of life. The VA decline coincided with migration of the TZ near the foveal center. There were outer retinal tubulations in degenerated, nonatrophic retina in the majority (69%) of patients. In general, RPE abnormalities paralleled photoreceptor degeneration, although there were regions with detectable but abnormally thin ONL co-localizing with severe RPE depigmentation and choroidal thinning.
Abnormalities of the POS and rod dysfunction are the earliest central abnormalities observed in CHM. Foveal function is relatively preserved until the fifth decade of life. Migration of the TZs to the foveal center with foveal thinning and structural disorganization heralded central VA loss. The relationships established may help outline the eligibility criteria and outcome measures for clinical trials for CHM.
A case study of choroideremia carrier – Use of multi-spectral imaging in highlighting clinical features
2016, American Journal of Ophthalmology Case Reports
Citation Excerpt :
This corresponds to the peripapillary atrophy seen in this case. Grover S et al. [13] reported normal visual field results in 6 CHM carriers who had fundus abnormalities. Another study showed a dense central scotoma on Humphrey visual fields testing in a case of a CHM carrier with severe unilateral central vision loss [11].
To report the use of non-invasive multi-spectral imaging of a female choroideremia (CHM) carrier with mild visual symptoms and extensive fundus mottling.
This was an observational case report study. A symptomatic 42-year-old female with a history of binocular CHM presented for routine ocular examination and underwent review of her clinical and photographic records, optical coherence tomography (OCT), intravenous fluorescein angiography (IVFA) and multi-spectral imaging (MSI). Dilated fundus examination and photography revealed similar outcomes of diffuse mottling with normal looking vessels. IVFA showed large irregular and confluent patches of RPE atrophy in the peripapillary and parapapillary areas as well as the midperiphery, corresponding to the OCT findings. The entire range of MSI imaging (520–940 nm) clearly illustrated the anomalies of the fundus including retinal pigment epithelium (RPE) mottling with melanin clumping not readily seen with the other imaging modalities. MSI fundus autofluorescence (MSI-FAF) showed a spotty hypo and hyperautofluorescent appearance of the fundus, consistent with the observations seen on IVFA and OCT images.
MSI significantly improves visualization of the retinal pigment epithelium in choroideremia. The non-invasive nature of MSI technique is a valuable tool in monitoring the effect of retinal and choroidal presentation in patients with CHM.
History of ocular straylight measurement: A review
2013, Zeitschrift fur Medizinische Physik
Citation Excerpt :
No positive functional effects were found in these patients, in particular no suppression of straylight. Alexander and coworkers found that patients with RP or choroideremia, who had minimal or no lens opacities by slit-lamp evaluation, also showed increased straylight levels, caused, they speculated, by subclinical changes in the PSC region of the lens as a consequence of photoreceptor cell degeneration [155–157]. A note of clinical significance must be made here.
The earliest studies on ‘disability glare’ date from the early 20^th century. The condition was defined as the negative effect on visual function of a bright light located at some distance in the visual field. It was found that for larger angles (>1degree) the functional effect corresponded precisely to the effect of a light with a luminosity equal to that of the light that is perceived spreading around such a bright source. This perceived spreading of light was called straylight and by international standard disability glare was defined as identical to straylight. The phenomenon was recognized in the ophthalmological community as an important aspect of the quality of vision and attempts were made to design instruments to measure it. This must not be confused with instruments that assess light spreading over small distances (<1 degree), as originating from (higher order) aberrations and defocus. In recent years a new instrument has gained acceptance (C-Quant) for objective and controllable assessment of straylight in the clinical setting. This overview provides a sketch of the historical development of straylight measurement, as well as the results of studies on the origins of straylight (or disability glare) in the normal eye, and on findings on cataract (surgery) and corneal conditions.
Am Anfang des 20. Jahrhunderts wurden umfangreiche Untersuchungen zur „physiologischen Blendung“ durchgeführt, definiert als die Beeinträchtigung des Sehens durch eine helle Lichtquelle, die in einem bestimmten Abstand innerhalb des Gesichtsfelds gelegen ist. Es wurde herausgefunden, dass für größere Winkel (>1Grad) der Funktionseffekt genau dem Effekt eines Lichtes mit einer Helligkeit entsprach, die der des Lichtes gleich ist, das als um eine solche helle Quelle herum sich ausbreitend wahrgenommen wird. Dieses um eine Lichtquelle herum wahrgenommene Licht wurde Streulicht genannt und als internationaler Standard wurde die physiologische Blendung als identisch zum Streulicht definiert. Das Phänomen wurde in der ophthalmologischen Gemeinschaft als wichtiger Aspekt der Qualität des Sehens erkannt und es wurde versucht, Instrumente zu entwerfen, um sie zu messen. Die Instrumente zur Streulichtmessung dürfen nicht mit solchen Instrumenten verwechselt werden, die sich in kleinem Winkel (<1 Grad) ausbreitendes Licht messen, welches durch Aberrationen (höherer Ordnung) und Defokussierung entsteht. Seit einigen Jahren gibt es ein Instrument (C-Quant) zur objektiven und kontrollierbaren Bestimmung von okularem Streulicht in der Klinik. In diesem Überblick werden die historische Entwicklung der Messung des okularen Streulichts, der Untersuchungen zum Ursprung von Streulicht (oder physiologischer Blendung) im normalen Auge sowie die Ergebnisse für Katarakte (Chirurgie) und Korneakonditionen skizziert.
Straylight values after refractive surgery: Screening for ocular fitness in demanding professions
2011, Ophthalmology
To study straylight testing as a screening method for ocular fitness after refractive surgery in demanding professions and to determine the distribution of elevations in straylight as a result of refractive surgery in a non-research setting in contrast with earlier reports in research settings.
Cross-sectional study.
The refractive surgery population consisted of 373 eyes in 198 subjects with a history of refractive surgery. The reference population consisted of 402 eyes in 214 young individuals without a history of refractive surgery.
Data were collected as part of routine testing at The Queen Astrid Military Hospital (Belgium), an independent military institution responsible for medical fitness examinations. Intraocular straylight was measured with the commercially available C-Quant instrument (Oculus Optikgeräte GmbH, Wetzlar, Germany), using the psychophysical compensation comparison (CC) method. Fellow eyes were compared to evaluate methodological aspects. The prevalence of impairment was evaluated for 2 age-independent cutoff criteria, a 2.0-fold and 3.2-fold increase, and an age-dependent cutoff criterion corresponding to an increase of 0.20 log units.
Methodological aspects such as repeatability, systematic differences, and distance to impaired scores, and prevalence of impaired straylight values after refractive surgery using proposed cutoff criteria.
The CC method exhibited good repeatability, and the chance of impaired scores due to variability in measurement was small. The prevalence of impaired straylight values was minimal in the reference population. In the refractive population, 9% (33/373) of values were above the factor 2.0 criterion, 2% (7/373) were above the factor 3.2 criterion, and 12% (45/373) were 0.20 log units above the age reference.
Straylight testing is a viable screening method for ocular fitness after refractive surgery. Patients from the general population who have undergone refractive surgery have significant elevations more frequently than surgery populations from high-quality research centers.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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^☆: Supported by research grant EY08301 (KRA) and core grant EY01792 from the National Eye Institute, National Institutes of Health, Bethesda, MD; a center grant from the Foundation Fighting Blindness, Hunt Valley, Maryland (GAF); and an unrestricted grant from Research to Prevent Blindness, provided to the Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago.

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Comparison of intraocular light scatter in carriers of choroideremia and X-linked retinitis pigmentosa☆

Abstract

Objective

Design

Participants

Main outcome measures

Results

Conclusions

Section snippets

Materials and methods

Results

Discussion

Vision Res

Ophthalmology

Exp Eye Res

Am J Ophthalmol

Ophthalmology

Exp Eye Res

Exp Eye Res

Exp Eye Res

The internalization of posterior subcapsular cataracts (PSCs) in Royal College of Surgeons (RCS) ratsII. The inter-relationship of optical quality and structure as a function of age

Mol Vis