American Academy of Optometry Annual Meeting: 2015 New Orleans Grand Rounds Submission Michael Yapp B.Optom (Hons), M.Optom, GradCertOcTher, FAAO Centre for Eye Health UNSW, Australia [email protected] Ph: +61 2 8115 0732

Abstract X-linked Retinoschisis presents early in life with an estimated prevalence of between 1:5000 and 1:20 000. Two congenitally unrelated cases are presented highlighting and contrasting the multimodal imaging differences between early and late stage disease to assist clinicians with their differential diagnosis and management of the condition.

I. Case History  Demographics o 16 and 47yo Caucasian males  Chief Complaints o 16yo: aware of reduced vision from the age of 5 but has not been given a reason . Denied any problems at school but has large handwriting and holds print very close to read o 47yo: Routine check-up for X-Linked Retinoschisis: has not been examined for approximately 5 years.  Ocular History o 16yo: Investigated at a public hospital clinic following a school screening at the age of 5 but has not had regular checks since o 47yo: Diagnosed at aged 7 . Reported unchanged vision since childhood apart from recent presbyopia . Patching amblyopia therapy at age 8yo  Medical History o 16yo: Unremarkable o 47yo: Smoker, hypercholesterolaemia.  Medications o 16yo: None o 47yo: Crestor  Other Salient information o 16yo: Brother and maternal uncle reportedly have good vision o 47yo: Cousin, brother and maternal uncle all affected.

II. Pertinent findings  Clinical 16yo: o Entering aided acuities were 6/15-2 OD and 6/19+2 OS.

o Humphrey 30-2 SITA-Fast Perimetry showed a generalised visual field loss OU with a MD of -5.87dB OD and -6.02dB OS, with more markedly depressed points superiorly in each eye. o Amsler grid was unremarkable in each eye. o Monocular colour vision with Standard D-15 was passed with each eye whereas L'Anthony Desaturated D-15 was failed (OD 2 crossings, OS 3 crossings, axis non- specific). o Contrast sensitivity was reduced in each eye at 1.60 units OD and 1.60 units OS with the MARS test (normal range 1.72 to 1.92 log units for adults < 60 years of age). o Funduscopy, retinal photography, Optomap imaging and Spectralis OCT revealed retinoschisis of both the inner and outer nuclear layers involving the entire posterior pole in each eye, most marked in the macular area. The macula exhibited a radial spoke pattern consistent with X-linked juvenile retinoschisis. o Spectralis OCT imaging through the posterior pole revealed extensive retinoschisis of the inner nuclear and outer nuclear layers at the posterior pole. The retinoschisis cavities had coalesced within the foveal area in each eye to form a cyst-like cavity. Autofluorescence revealed a star-like pattern of hyperfluorescence surrounded by hypofluorescence, which was symmetrical OU. o Cirrus OCT Macula thickness analysis showed a marked thickening of each macula compared to the expected pattern.

47yo: o Entering aided acuities were 6/38-2 OD and 6/12-1 OS with no improvement to pinhole in either eye. o Amsler grid was complicated in the right eye by the poor acuity however no distortions or 'missing' areas were reported. The left was reported as showing patches of less distinct squares. o Colour vision was failed with 9 mostly tritan crossings OD and 4 tritan crossings OS with the Standard D-15. o Contrast sensitivity was symmetrical but notably below average at 1.20 units OD and OS with the MARS test (normal range 1.72 to 1.92 log units). o Funduscopy, Retinal photography, Optomap imaging and Spectralis OCT revealed a ring of hypoflouresence around both maculae as well as a loss of the typical foveal hypofluoresence. There was a marked schisis extending from inferior to the right disc to the periphery with notable vitreous traction and dendritiiform vessels as well as areas of chorioretinal atrophy. The right peripheral retina also showed abnormal vitreo-retinal adhesions. o Both maculae showed a notable loss of the outer nuclear and photoreceptor layers with mottling of the RPE. There was an isolated area of schisis at the right fovea and a confluent area in the left with the loss of the foveal pit in both. o The NRR appeared healthy with an area of pigment mottling and PPA inferior to the right disc.

o Cirrus OCT showed the macula thickness in each eye was markedly thinner than normal in all sectors of both eyes apart from the central sector of the left which was affected by the persistent schisis. o An RNFL assessment was affected by errors in instrument segmentation.

 Laboratory studies o N/A  Radiology studies o N/A  Others o N/A

III. Differential diagnosis  Primary/leading o X-Linked retinoschisis  Others o Myopic foveoschisis, Cystoid Macular Oedema, Butterfly- shaped macular dystrophy, Stargardt’s disease, Stickler Syndrome, Goldmann-Favre Syndrome

IV. Diagnosis and discussion  Elaborate on the condition and unique features o X-linked retinoschisis affects males early in life with an estimated prevalence of between 1:500 and 1:20,000 o Hallmark features in patient under 30 include a spoke- wheel pattern at the macula with features such as peripheral dentritiform vessels showing typically later in life o Visual acuity reduction is markedly variable between patients but is typically relatively stable until the 5th decade when it reduced in conjunction with macular atrophy o Retinal detachments have been reported in between 5 and 22% of patients o Vitreous haemorrhages occur in between 4 and 40% of patients o Macular holes, neovascular glaucoma, vitreo-retinal traction with secondary macular dragging and optic atrophy have also been reported. o Expression of the gene is typically symmetrical with female carriers asymptomatic but occasionally showing minor retinal abnormalities o Research suggests a mutation in the RS1 gene which encodes retinoschisin. To date 191 different mutations in this gene have been identified

V. Treatment, management  Treatment and response to treatment o Treatment of the schisis is generally not indicated due to an increased risk of retinal detachment with treatment therefore limited to complications such as those mentioned above. . Referral of the 16 year old to a retinal specialist was initiated for an initial examination as well as to discuss genetic counselling as needed o Illumination and Low vision is critical to maximising the patient’s quality of life. . 16yo claimed that he had no current visual complaints however a detailed discussion was had with both him and his parents to ensure that symptoms were identified and managed as soon as needed.  Review in 6 months was scheduled due to his staging at school and likely increased workload in the near future . 47yo felt that his vision was unchanged and happy with his current visual performance.  Annual review was instigated

 Bibliography o Molday et al. X-Linked juvenile retinoschisis: Clinical diagnosis, genetic analysis and molecular mechanisms. Progress in retinal and Eye Research 2012(31):195-212 o Tantri et al. X linked retinoschisis: a clinical and molecular genetic review. Survey of Ophthalmology 2004;49(2):214-230 o Yu et al. Foveomacular schisis in juvenile X-Linked retinoschisis: an optical coherence tomography study. American Journal of Ophthalmology 2010;149:973-978

VI. Conclusion  Clinical Pearls o Autofluoresence and OCT imaging can be diagnostic for X- linked juvenile retinoschisis o Close monitoring for evidence of progression utilising multimodal imaging will assist with management o Retinal detachments and vitreous haemorrhages are potential complications with a detailed peripheral retinal examination critical to management o Careful review of the patients visual symptoms and appropriate management using tints and aids may greatly assist in their quality of life