Ultrawide field imaging to document the progression of gyrate atrophy of the choroid and retina over 5 years

Abstract

A family of three siblings affected with gyrate atrophy of the choroid and retina is presented. Ultrawide field fundus imaging was used to monitor the progression of the disease objectively over 5 years.

Background

Gyrate atrophy of the choroid and retina (GACR) is a rare disease, inherited as an autosomal recessive trait.¹ The biochemical abnormality includes deficiency of pyridoxal-dependent mitochondrial enzyme ornithine delta aminotransferase which increases plasma ornithine concentration.¹ Ultrawide field fundus imaging (UWFI) (Optos, Marlborough, Massachusetts, USA) uses pseudocolour image of the fundus of up to 82% or 200 degrees, as compared with conventional fundus cameras with field capturing capacity of up to 30 and 50 degrees, with a maximum of 140 degrees with montage.² In choroidal dystrophies, UWFI helps to evaluate the fundus in a single panoramic view.³ Early lesions in the peripheral retina can be picked up by UWFI.^{3 4}

In this report, we present a case series of three siblings^{3 5} who had typical peripheral chorioretinal atrophic lesions of gyrate atrophy. Plasma ornithine was tested in the eldest sibling and came out to be highly elevated (776.7 nmol/mL (reference value 10–163 nmol/mL)).³ They were advised arginine-restricted diet and oral pyridoxine. However, patient compliance was compromised in all cases due to financial constraints. A follow-up of 5 years showed progression of the disease with an increase in the areas of chorioretinal atrophy in the periphery in all three siblings. UWFI was used to objectively monitor the progression of the disease.

Case presentation

Case 1

The youngest sibling, a 10-year-old boy, had the best-corrected visual acuity (BCVA) of 6/18p in the right eye (RE, –6.5/–2.5×15°) and 6/18 in the left eye (LE, –7.5/–2.0×160°) at the last follow-up. BCVA was 6/12 in both eyes (BE) 5 years ago. Anterior segment and intraocular pressure (IOP) were normal. Initially, there were only a few sharply demarcated areas of focal chorioretinal atrophy in BE, which had considerably increased over 5 years (figure 1A, B). On optical coherence tomography (OCT) (swept-source OCT DRI OCT Triton, Topcon, Tokyo, Japan), BE at the last follow-up showed foveoschisis with central macular thicknesses (CMTs) of 361 microns (RE) and 378 microns (LE) (figure 1D). OCT of the macula (figure 1C, Spectralis HRA+OCT, Heidelberg Engineering GmbH, Heidelberg, Germany) of BE done 5 years ago³ did not show any evidence of intraretinal hyporeflective areas with CMTs of 271 microns (RE) and 259 microns (LE). The ultrawide field fundus autofluorescence (UWF-FAF) showed hypoautofluorescence at the scalloped areas (figure 2A, B).

Figure 1.

Ultrawide field fundus image of case 1, 5 years ago (A) and current image (B). Optical coherence tomography of the macula of the same eye 5 years ago (C) and at the last follow-up (D).

Figure 2.

The ultrawide field fundus autofluorescence images of case 1 (A, B), case 2 (C, D) and case 3 (E, F).

Case 2

His elder sister, a 12-year-old girl, had BCVA of 6/24 (RE, –6.25/–2.5×10°) and 6/24 (LE, –6.25/–2.5×170°) at the last follow-up. Five years ago, the BCVA were 6/36 (RE) and 6/24 (LE).³ Anterior segment and IOP were normal. There are sharply demarcated areas of focal chorioretinal atrophy that had become more confluent in BE at the last follow-up (figure 3A, B). The gaps between the scalloped areas had reduced and lesions had progressed more posteriorly. The CMTs were 338 microns (RE) and 296 microns (LE) (Topcon DRI OCT Triton) improving from 558 microns (RE) and 431 microns (LE) (Spectralis OCT), respectively, 5 years ago (figure 3C, D).³ UWF-FAF revealed a small central area of preserved autofluorescence (figures 2D and 4C).

Figure 3.

Ultrawide field fundus image of case 2 5 years ago (A) and current image (B). Optical coherence tomography of the macula of the same eye 5 years ago (C) and at the last follow-up (D).

Figure 4.

Ultrawide field fundus image of case 3, 5 years ago (A) and current image (B). Optical coherence tomography of the macula of the same eye 5 years ago (C) and at the last follow-up (D).

Case 3

The eldest brother, a 13-year-old boy, had a BCVA of 6/18 in both eyes (–14.5/–0.5×15° in RE, –12.5/–1.5×170° in LE) at the last follow-up. BCVA noted 5 years ago were 6/36 (RE) and 6/24 (LE).³ Anterior segment and IOP were normal. There was no squint of nystagmus. The sharply demarcated areas of focal chorioretinal atrophy in BE had considerably increased over 5 years and approached centrally (figure 4A, B).³ The most recent CMTs (Topcon DRI OCT Triton) was 391 microns (RE) and 397 microns (LE) compared with 308 (RE) and 333 microns (LE) 5 years ago (Spectralis OCT) (figure 4C, D). Fundus autofluorescence photos demonstrated preserved autofluorescence at the macula and an area nasal to the optic disc (figure 2E, F).

Outcome and follow-up

The family is scheduled for follow-up after 3 months.

Discussion

GACR is a progressive disease and the progression in some patients may be reduced with pyridoxine (vitamin B₆ 120–600 mg/day) supplementation and arginine-restricted diet.¹ Takki⁶ analysed 15 cases of GACR from Finland and proposed four stages of the disease.

Stage I

This stage was noted in the two youngest patients (boys aged 9 and 10 years, respectively) in the series by Takki.⁶ This was characterised by few round scalloped well-demarcated round areas of chorioretinal atrophy which were usually separate but coalesced at some places. Choroidal vessels were easily seen through the surrounding translucent retinal pigment epithelium.⁶ The optic disc, macula and retinal vasculature are unremarkable and there is concentric visual field limitation.⁶ Case 1 in our series was in this stage 5 years ago.

Stage II

This stage was characterised by an increase in the size of garland-shaped scalloped areas of chorioretinal atrophy, their coalescence and advancement towards the macula. The visual field became narrower and attenuation of retinal vessels was noted compared with stage I. An ‘initial degeneration around the disc’ was noted.⁶ Case 1 of our series seems to be in this stage currently.

Stage III

There was a degenerative area around the optic disc. Areas of normal-appearing retina were noted in the macula, in an annular area between the degeneration of the disc and mid-peripheral confluent area of degeneration, and at the extreme peripheral retina.⁶ Velvet-like granular appearance was noted in these areas which were still not affected by the degeneration. The optic nerve was paler and retinal vessels were narrower than in earlier stages. The visual field showed an island of central visual field and an annular zone of present visual function corresponding to the annular area of the uninvolved retina.⁶ Case 2 and case 3 in our series appear to fall into this stage except for the fact that there was no annular area of normal-appearing retina around the arcades.

Stage IV

This is the most advanced stage characterised by an atrophic posterior pole except a small island of the functioning macula. The vessels were severely narrowed but optic atrophy or bone corpuscle pigmentation was not seen. However, granular pigmentation was noted around the equator and colourless, glittering crystals were noted around the equator.⁶

In our series, the fundus features and areas of chorioretinal atrophy progressed in all patients. However, a spontaneous improvement in the macular status with a reduction in CMT was noted in case 2. Important limitation was that, the OCT images were captured using different machines. Spontaneous resolution of foveoschisis has been reported in X-linked retinoschisis.^{7 8} Fluctuation of the CMT in cases with foveoschisis in retinitis pigmentosa can also be noted (personal experience). Our patients were non-compliant with arginine-restricted diet, pyridoxine and topical dorzolamide. Thus, the changes seen may denote the natural history of GACR.

GACR is known to be associated with central macular changes like cystoid macular oedema, choroidal neovascular membrane, epiretinal membrane and foveoschisis.^{1 3 9} The patients in our series had intraretinal hyporeflective spaces, and a petaloid leak on fluorescein angiogram was not noted giving the diagnosis of foveoschisis. All cases maintained a BCVA of 6/36 or better, although the chorioretinal atrophy progressed more posteriorly which was documented by UWFI. In 1978, Berson et al¹⁰ showed slight enlargement over 2 years of gyrate atrophy lesions in the peripapillary area and temporal mid-periphery in a 12-year-old girl using a standard fundus camera. In 1981, Takki and Milton reported mild progression to be detected as early as over 2 years in 29 Finnish patients with GACR using manual time-consuming fundus montages.¹⁰ More recently in 2016, Salcedo-Villanueva et al used UWFI in a daughter and a mother with GACR to record mild disease progression over 2 years.¹¹ Hereby, we showed a striking marked disease progression over 5 years in three siblings. UWFI may be useful in objectively and swiftly documenting peripheral retinal disorders including retinal vascular disorders, peripheral retinal disorders, posterior segment tumors, hereditary posterior segment diseases and uveitis.^{4 12}

Limitations of this report include the non-availability of genetic confirmation, visual fields and follow-up fluorescein angiography images. We did not have the UWF-FAF images at presentation. OCT images captured using different machines may not be comparable.

In conclusion, we report the UWFI documentation of the progression of disease in GACR.

Learning points.

• Gyrate atrophy of the choroid and retina (GACR) is progressive chorioretinal dystrophy.

• Ultrawide field fundus imaging (UWFI) is a promising modality that can image most of the posterior segment in a single capture.

• UWFI can be used to objectively monitor the progression of diseases involving a large area of the retina including GACR.

Ethics statements

Patient consent for publication

Parents/guardians consent obtained.