CLINICAL SCIENCES Abnormal Foveal Morphology in Ocular Albinism Imaged With Spectral-Domain Optical Coherence Tomography Gabriel T. Chong, MD; Sina Farsiu, PhD; Sharon F. Freedman, MD; Neeru Sarin, MBBS; Anjum F. Koreishi, BS; Joseph A. Izatt, PhD; Cynthia A. Toth, MD Objectives: To evaluate the spectrum of foveal archi- Pudlak syndrome: persistence of an abnormal, highly tecture in pediatric albinism and to assess the utility of reflective band across the fovea, multiple inner retinal spectral-domain optical coherence tomography (OCT) layers normally absent at the center of the fovea, and loss in ocular imaging of children with nystagmus. of the normally thickened photoreceptor nuclear layer at the fovea when compared with that in control sub- Methods: Spectral-domain OCT imaging was per- jects. The optic nerve was elevated in multiple eyes formed on study subjects in 3 groups: subjects with of subjects with OA or suspected OA and the subject ocular albinism (OA) or suspected OA with foveal hypo- with oculocutaneous albinism and Hermansky-Pudlak plasia, with nystagmus, and with or without iris trans- syndrome. illumination; a subject with oculocutaneous albinism and Hermansky-Pudlak syndrome; and control subjects. Dense Conclusions: A spectrum of foveal morphological ab- volumetric scans of each fovea were captured using stan- normalities is seen in subjects with OA or suspected OA, dard and handheld spectral-domain OCT devices. Im- which in some cases contrasted with previous studies ages were postprocessed and scored for the presence and using time-domain OCT. These OCT findings clarify configuration of each retinal layer across the fovea. the morphology of foveal hypoplasia seen clinically. Results: High-quality spectral-domain OCT images ob- This imaging modality may be useful in evaluating tained from each subject revealed a range of abnormali- children. ties in subjects with OA or suspected OA and the sub- ject with oculocutaneous albinism and Hermansky- Arch Ophthalmol. 2009;127(1):37-44 CULAR ALBINISM (OA) IS graded, while at the same time with fo- a genetic disorder of veal hypoplasia, central vision should be melanin production that diminished owing to widely spaced cen- occurs with a frequency tral cones.4,8,9 of about 1 in 50 000 per- The nystagmus seen in albinism usu- Osons in the United States.1 In contrast to ally manifests by age 2 or 3 months and oculocutaneous albinism (OCA) involv- often lessens with age and near vision as ing skin, hair, and eyes, OA is limited to a result of convergence.10 Nystagmus is the eyes.2 Ocular albinism type 1 is an in- probably due to the foveal hypoplasia (ab- herited X-linked disease causing ocular sent foveal pit on light microscopy) and clinical features that may include nystag- the aberrant visual pathways seen in pa- mus, decreased visual acuity, hypopig- tients with albinism.3,10 In addition, astig- mentation of the retina, foveal hypopla- matism and other refractive errors are com- sia, translucency of the iris, macular mon and could lead to some degree of transparency, photophobia, and abnor- amblyopia and low visual acuity.4 Owing mal neuronal wiring (abnormal decussa- to misrouting of the optic pathways, pa- Author Affiliations: tion of nerve fibers at the chiasm).3-5 The tients with OA are at high risk for strabis- Departments of Ophthalmology decreased visual acuity varies, and re- mus and loss of stereovision.4 (Drs Chong, Farsiu, Freedman, ports suggest that visual acuity is re- The genetics involved in OCA type 1 Sarin, Izatt, and Toth and duced to 20/25 to 20/200.6-8 It is possible (OCA1) focus on mutations in the tyrosi- Mr Koreishi) and Biomedical 2 Engineering (Drs Izatt and that with decreased pigmentation, light en- nase gene. Those individuals who lack Toth), Duke University, tering the eye is more prone to scattering pigment owing to complete inactivity of Durham, North Carolina. and the resulting retinal image is de- the tyrosinase gene have OCA1A, whereas (REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 1), JAN 2009 WWW.ARCHOPHTHALMOL.COM 37 ©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 those with mutations in the tyrosinase gene that allow ing other ophthalmic imaging studies performed at Duke Uni- residual enzyme activity have OCA1B. Individuals have versity Eye Center. Study subjects were examined by a pedi- OCA2, OCA3, and OCA4 when there is a mutation in atric ophthalmologist (S.F.F.). Clinical examination included the P-gene on chromosome 15q, the tyrosine-related pro- best-corrected visual acuity, presence and type of manifest nys- tein 1 gene, or the membrane-associated transporter gene, tagmus, skin color, hair color, iris color, and presence or ab- sence of transillumination defects (assessed in a darkened room respectively.2 Hermansky-Pudlak syndrome (HPS), caused with the subject sitting at a slitlamp biomicroscope unless the by mutations in 1 of 7 HPS genes, and Che´diak-Higashi child could not sit at the table-mounted slitlamp biomicro- syndrome, caused by a mutation in the lysosomal- scope, in which case a portable slitlamp was used). Fundus ex- trafficking regulator gene, are multisystemic disorders as- amination was performed with an indirect ophthalmoscope and sociated with OCA.3 Except for OCA1A, individuals with either a 20-diopter (D) or 28-D condensing lens. Skin biopsy the conditions described earlier may have some pig- and/or genetic testing were not performed in subjects with OA ment in the skin, hair, and irides. or suspected OA or control subjects in this study. The subject Optical coherence tomography (OCT) is the optical with OCA and HPS was diagnosed previously by genetic test- analogue to ultrasonography and measures the echo time ing. Subjects with foveal hypoplasia (determined clinically via delay and magnitude of reflected or backscattered light visualization with indirect ophthalmoscopy using a 20-D lens, using low-coherence interferometry.11 Cross-sectional im- looking for absence of the foveal pit), with nystagmus on clini- ages are obtained by measuring the backscattered light cal examination, and with or without iris transillumination de- fects were included in the group with OA or suspected OA. Con- while scanning across multiple sites in a transverse fash- trol subjects were white, were aged between 5 and 11 years, ion. The data obtained are displayed as false-color or gray- had normal skin and hair pigmentation, had 20/20 visual acu- scale images. ity in each eye, and lacked nystagmus. The subject with OCA A conventional time-domain (TD) OCT system (Stra- had a diagnosis of HPS. This subject was chosen as a positive tus OCT; Carl Zeiss Meditec, Dublin, California) can pro- control to verify the findings of OCA when compared with the vide 8- to 10-µm axial resolution and 512 axial scans in subjects with suspected OA who did not clearly have albi- 1.3 seconds.11 Clinical limitations of the relatively slow nism. As the subject with OCA and HPS was already sched- standard TD-OCT are partially due to the subject’s eye uled to undergo anesthesia for strabismus surgery, imaging un- motion, which can lead to image artifacts. Such artifacts der anesthesia allowed for the entire posterior pole to be imaged may be reduced by exploiting cross-correlation algo- under controlled conditions to ensure that the area where the fovea might be located would not be inadvertently bypassed rithms that automatically align adjacent axial scans and 11 during SD-OCT imaging. with eye-tracking protocols. Ultrahigh-resolution OCT The retinas of both eyes of the study subjects were then imaging with axial resolutions of 2 to 3 µm has been used scanned using SD-OCT, and the eye with the best images, either to demonstrate retinal morphology with improved de- right or left, was used for analysis. The subject with known OCA tail. Unfortunately, ultrahigh-resolution OCT is even also had SD-OCT imaging of each retina performed while su- slower than the TD systems, where scanning speeds are pine during scheduled anesthesia for strabismus surgery, and typically 150 to 250 axial scans per second.11 Thus, im- SD-OCT was performed using a portable, handheld, noncon- age artifacts due to eye motion are more severe and cov- tact SD-OCT device (Bioptigen Inc, Research Triangle Park, erage is more restricted.11 North Carolina). To overcome such limitations, ophthalmic imaging re- We used an SD-OCT system developed by one of us (J.A.I.) with operating software provided by Bioptigen Inc that was re- search is now progressively relying on the novel (Fou- 11-13 fined for imaging patients with OA (in collaboration with rier) spectral-domain (SD) OCT systems. The SD- C.A.T.). The SD-OCT light source is a superluminescent di- OCT systems have a higher speed and a sensitivity ode (Superlum Diodes, Ltd, Carrigtwohill, County Cork, Ire- advantage over the conventional OCT systems (50 times land) with a central wavelength of 840 nm and a bandwidth of faster than standard TD-OCT and 100 times faster than 49 nm, yielding a theoretical axial resolution of 6.3 µm in air ultrahigh-resolution OCT imaging systems).11 Owing to and 4.6 µm in tissue. The lateral resolution of each A-scan was the increase in speed, a single cross-sectional scan of 1000 approximately 15 to 20 µm. The power incident on the study A-scans can be captured, processed, and displayed in about subject’s cornea was roughly 500 µW, which is well below the American National Standards Institute’s extended exposure limit 60 milliseconds. This reduces target motion artifacts, re- 14 sulting in a more stable captured image. This is espe- of 750 µW for 8 hours.