Relationship between foveal cone specialization and pit morphology in albinism.
OBJECTIVE
Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism.


METHODS
We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured.


RESULTS
We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism.


CONCLUSIONS
Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue.
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Melissa A
MA
Wilk
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
John T
JT
McAllister
Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States.
Robert F
RF
Cooper
Moorfields Eye Hospital, London, United Kingdom Institute of Ophthalmology, University College London, United Kingdom.
Adam M
AM
Dubis
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Teresa N
TN
Patitucci
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Phyllis
P
Summerfelt
Core Laboratory, Marshfield Clinic, Marshfield, Wisconsin, United States.
Jennifer L
JL
Anderson
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Kimberly E
KE
Stepien
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Deborah M
DM
Costakos
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Thomas B
TB
Connor
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
William J
WJ
Wirostko
Casey Eye Institute Molecular Diagnostics Laboratory, Portland, Oregon, United States.
Pei-Wen
PW
Chiang
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Alfredo
A
Dubra
Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama, United States.
Christine A
CA
Curcio
Center for Human Genetics, Marshfield Clinic, Marshfield, Wisconsin, United States.
Murray H
MH
Brilliant
Departments of Ophthalmology and Visual Neurosciences and Pediatrics, University of Minnesota, Minneapolis, Minnesota, United States.
C Gail
CG
Summers
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Joseph
J
Carroll
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016115:Albinism, Oculocutaneous / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D002452:Cell Count; D002648:Child; D004247:DNA / Q000235:genetics; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005584:Fovea Centralis / Q000473:pathology* / Q000503:physiopathology; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009887:Ophthalmoscopy; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D055815:Young Adult
D005136:Eye Proteins; D004247:DNA
adaptive optics; albinism; foveal development; foveal morphology