Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and central vision in later life because of progressive loss of rod and cone photoreceptor cells. Measures of retinal function, such as the electroretinogram, show that photoreceptor function is diminished generally many years before symptomic night blindness, visual-field scotomas, or decreased visual acuity arise. More than 45 genes for retinitis pigmentosa have been identified. These genes account for only about 60% of all patients; the remainder have defects in as yet unidentified genes. Findings of controlled trials indicate that nutritional interventions, including vitamin A palmitate and omega-3-rich fish, slow progression of disease in many patients. Imminent treatments for retinitis pigmentosa are greatly anticipated, especially for genetically defined subsets of patients, because of newly identified genes, growing knowledge of affected biochemical pathways, and development of animal models.

We describe two families with retinitis pigmentosa (RP), a hereditary neurodegeneration of rod and cone photoreceptors in the retina, in which affected members were homozygotes for loss-of-function mutations in the IDH3B gene encoding the beta subunit of NAD-specific isocitrate dehydrogenase (NAD-IDH), the enzyme believed to catalyze the oxidation of isocitrate to α-ketoglutarate in the citric acid cycle. Cells from the affected family members had a substantial reduction of NAD-IDH activity with about a 300-fold increase in the Km for NAD. NADP-specific isocitrate dehydrogenase (NADP-IDH), an enzyme that can catalyze the same reaction, was normal. The patients had no health problems associated with the enzyme deficiency except for RP. The existence of these patients supports the hypothesis that mitochondrial NADP-specific IDH, rather than NAD-IDH, can serve as the major catalyst for this reaction in the citric acid cycle outside the retina, and that the retina has a particular requirement for NAD-IDH.Mutations in at least 34 genes have been identified as causes of nonsyndromic RP, including 15 dominant genes, 20 recessive genes, and 2 X-linked genes (RetNet website). The identified RP genes are estimated to account for about 60% of cases 1 . In addition, 11 unidentified genes have been mapped to specific chromosomal regions. It is estimated that there are dozens of still unmapped, unidentified recessive RP genes, each accounting for at most a few percent of cases 1, 2 .The approach we used to search for some of the unidentified recessive RP genes depends on the fact that recessive alleles are often deletions, frameshift mutations, or nonsense mutations that result in a scarcity of the disease gene's transcript either because the transcript is not made Correspondence to: Thaddeus P. Dryja, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114; Thaddeus.dryja@novartis.com. * Current affiliation: University Medical Center Groningen, Groningen, The Netherlands § These authors contributed equally to the work AUTHOR CONTRIBUTIONS D.T.H., T.L.M., and T.P.D. designed and conducted the molecular genetic analyses. E.L.B. clinically evaluated, selected, and recruited patients and their family members, as well as helped in the design of the study. M.D. and R.F.C. designed and conducted the enzyme assays. All authors discussed and interpreted the results and wrote the manuscript. or is rapidly degraded due to nonsense-mediated decay 3 . The principle underlying this method has been previously described 4, 5, 6 , but, as far as we know, the method has never been used to identify a novel gene causing a hereditary disease. Using microarray techniques that simultaneously assay mRNA levels from tens of thousands of transcripts in individual patients, we searched for genes with absent or very low expression that may be due to two allelic diseasecausing mutations. While it would have been ideal to carry out the analysis with RNA derived from the retina prior to its degeneration, this tissue is not availa...

Using NVGs seems to improve nighttime mobility in dark outdoor conditions by decreasing unintended contacts with obstacles and increasing walking speed. Use of NVGs increased independent activities in these subjects and was generally positively evaluated for everyday outdoor use.

PurposeTo investigate the current practice of enucleation with or without orbital implant for retinoblastoma in countries across the world.MethodsA digital survey identifying operation techniques and material used for orbital implants after enucleation in patients with retinoblastoma.ResultsWe received a response of 58 surgeons in 32 different countries. A primary artificial implant is routinely inserted by 42 (72.4%) surgeons. Ten (17.2%) surgeons leave the socket empty, three (5.2%) decide per case. Other surgeons insert a dermis fat graft as a standard primary implant (n=1), or fill the socket in a standard secondary procedure (n=2; one uses dermis fat grafts and one artificial implants). The choice for porous implants was more frequent than for non-porous implants: 27 (58.7%) and 15 (32.6%), respectively. Both porous and non-porous implant types are used by 4 (8.7%) surgeons. Twenty-five surgeons (54.3%) insert bare implants, 11 (23.9%) use separate wrappings, eight (17.4%) use implants with prefab wrapping and two insert implants with and without wrapping depending on type of implant. Attachment of the muscles to the wrapping or implant (at various locations) is done by 31 (53.4%) surgeons. Eleven (19.0%) use a myoconjunctival technique, nine (15.5%) suture the muscles to each other and seven (12.1%) do not reattach the muscles. Measures to improve volume are implant exchange at an older age (n=4), the use of Restylane SQ (n=1) and osmotic expanders (n=1). Pegging is done by two surgeons.ConclusionNo (worldwide) consensus exists about the use of material and techniques for enucleation for the treatment of retinoblastoma. Considerations for the use of different techniques are discussed.

ABSTRACT.Purpose: To evaluate complications of different types of orbital implants following enucleation for retinoblastoma. Methods: We performed a retrospective chart study of all patients that underwent enucleation as treatment of retinoblastoma between April 1991 and June 2013. Events of implant exposure, extrusion (defined as a complete loss of the implant, or a major exposure that could not be closed) and socket abnormalities were analysed for association with implant type and influence of additional external beam radiation therapy (EBRT) and/or chemotherapy. Results: A total of 224 enucleations in 216 patients (eight bilateral) were identified. Mean age at surgery was 1.9 (median 1.5) years. Of the 219 included enucleated eyes, 20 were not replaced by a primary implant and 18 were replaced by an Allen implant. Scleral wrapped hydroxyapatite (HA) and acrylic implants (polymethylmethacrylate) were inserted in, respectively, 79 and 102 cases. In the total population, 29 treatment or implant-specific events (13.2%) were registered. Main complications were implant exposure n = 10 (4.6%) and extrusion n = 6 (2.7%). The acrylic/sclera group had less exposures or extrusions (5 of 102, 4.9%) compared to the HA/sclera group (10 of 79, 12.7%), although this difference did not quite reach statistical significance (p = 0.06). Additional treatment (chemotherapy and/or EBRT for the fellow eye) was administered in 78 cases (35.8%). The overall complication rate in the entire study population was significantly higher (16.7% versus 5.7%) in the group exposed to additional therapy (OR 3.3; 95% CI 1.30-8.36 p = 0.008). This negative effect of additional therapy was also significant in the combined acrylic/HA group (OR 2.9; 95% CI 0.97-8.46 p = 0.048). Conclusion: Our results suggest a favourable outcome for acrylic implants compared to the HA implant. Additional treatment with chemotherapy and/or EBRT is associated with an increased risk of complications.

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Careful history and examination can give some direction in the diagnostic procedure; however, PSP is probably multifactorial and the specific origin(s) may remain uncertain. Implant replacement can be an effective treatment. Studies to identifiy less invasive procedures are required.

Minor late and potentially treatable effects were seen in patients with implant. Larger sized implants were associated with a higher incidence of ptosis; implant size did not affect subjective outcome with respect to volume or prosthetic motility. Treatment with EBRT had a less favourable outcome.