X-linked retinoschisis: clinical phenotype and RS1 genotype in 86 UK patients.

BACKGROUND: Inactivating mutations of the gene RS1 lead to X-linked retinoschisis, a progressive retinal dystrophy characterised by schisis within the inner layers of the neuroretina. The mutation spectrum is large and the phenotype variable. AIM: To determine whether there is a correlation between mutation type and disease severity. METHODS: We identified the causative mutation in 86 affected patients and examined each of these patients in detail. Different categories of mutation were compared for each phenotypic characteristic. RESULTS: We found a reduction in visual acuity with increasing age and worsening macular pathology in patients over 30 years old (p < or = 0.001), but there was no correlation between mutation type and severity of disease. Furthermore, we found a wide variation in phenotype even within families. CONCLUSIONS: Identifying the causative mutation in patients with X-linked retinoschisis is helpful in confirming diagnosis and in counselling of family members but cannot be used to predict prognosis for an individual patient.

Foveal ectopia in X-linked retinoschisis.

BACKGROUND: This study compared the position of the foveal center in patients with X-linked retinoschisis (XLRS) and controls and estimated the frequency of foveal ectopia in XLRS. METHOD: Fundus photographs of 23 patients with XLRS and 25 controls were reviewed. The position of the foveal center relative to the vertical center of the optic disk was determined from magnified images and expressed as the angle between the disk and foveal centers, relative to the horizontal meridian. The shortest distance between the foveal and disk centers was also measured, using the horizontal disk diameter (HDD) as the relative size unit. RESULTS: The position of the foveal center could be determined accurately for 43 eyes of the 23 patients with XLRS. The foveal center was located an average of 4.7 degrees (standard deviation, 9.3) below and 3.2 HDD (standard deviation, 0.4) temporal to the vertical disk center. In 9 (21 %) of the eyes, the fovea was above the horizontal meridian. For the control eyes, the foveal center was an average of 7.8 degrees (standard deviation, 2.3) below and 2.9 HDD (standard deviation, 0.4) temporal to the vertical disk center. According to a previous definition, foveal ectopia was present in 13 (30%) of the eyes with XLRS and none of the control eyes (P < 0.001). CONCLUSION: Foveal ectopia occurs in at least 30% of eyes with XLRS. This finding may provide a useful diagnostic sign for XLRS and may have implications for its pathogenesis.

Micro syndrome in Muslim Pakistan children.

OBJECTIVE: To date, Micro syndrome has been reported in only three children from one family. We describe an additional 14 children from 11 families. DESIGN: Retrospective case series. PARTICIPANTS: Fourteen children from 11 families attending one of five British hospitals. MAIN OUTCOME MEASURES: The following features were documented: pre- and postoperative eye findings, electrophysiologic analysis, systemic abnormalities, development, neuroimaging, genealogy, geographic origin of family. RESULTS: We expand and modify the description of ocular and electrophysiologic findings in Micro syndrome. The eye findings of microphakia, microphthalmos, characteristic lens opacity, and atonic pupils were the presenting feature in all infants and were the most reliable diagnostic signs in the immediate postnatal period. Cortical visual impairment, microcephaly, and developmental delay were not always detectable initially; they developed in all children by 6 months of age. Microgenitalia were a useful diagnostic clue in affected males only. Therefore, eye features were more consistently useful in determining diagnosis than dysmorphology or brain imaging. The families of all the children originate from the Muslim population of Northern Pakistan. Inheritance is likely to be autosomal recessive. CONCLUSIONS: Micro syndrome usually presents to the ophthalmologist, who may be able to make the diagnosis on the basis of characteristic eye findings combined with ethnic origin. Initially, the nature and severity of nonophthalmic features are not apparent. Early diagnosis of the underlying condition is important to guide management of the cataracts, glaucoma, and developmental delay. It is helpful for the family and medical staff to be aware of the low level of vision that develops despite optimal ophthalmic intervention. Genetic counseling extending into the wider family is particularly important in view of the high rate of consanguinity.

Who should manage primary retinal detachments?

PURPOSE: To determine whether the outcome of primary retinal reattachment surgery in a subregion is improved by surgery being performed in a specialist vitreoretinal unit (VRU). METHODS: A subregional, population-based, retrospective audit cycle of primary retinal reattachment surgery was conducted by independent investigators. The subregion was defined as the catchment area of a teaching hospital (TH) with a specialist VRU and three neighbouring district general hospitals (DGHs). During the initial audit period (January 1989 to December 1990), 142 cases were treated at all four hospitals: TH/VRU (83), DGH-A (15), DGH-B (13), and DGH-C (31). Policy changes after the initial audit led to primary retinal reattachment surgery being predominantly performed by the VRU. During the re-audit period (September 1995 to August 1997), 160 cases were treated at two hospitals: VRU (148) and DGH-C (12). The outcome measure employed was complete retinal reattachment after a single procedure with a minimum follow-up of 12 months. RESULTS: The success rate for primary retinal reattachment surgery in the subregion improved from 76.1% to 88.8% (p = 0.006) following the policy changes. The success rate of the vitreoretinal specialists in the VRU (90%) was greater than the general ophthalmologists in the DGHs (ranging from 47% to 77%), despite case selection by the general ophthalmologists. The number of cases treated by the VRU increased by 156% in the 6.5 year interval between the two audits due to a widespread change in the model of care for primary retinal detachments (both within and outside the subregion). During the re-audit period, the VRU treated 348 primary retinal detachments (including referrals from outside the subregion), achieving a success rate of 86.8% with a single procedure and 97.4% with further surgery. This primary success rate included 35 cases (10%) treated by vitrectomy with silicone oil tamponade who did not undergo silicone oil removal. CONCLUSIONS: The outcome of primary retinal reattachment surgery can be improved if surgery is performed by a specialist VRU. It is suggested that the current standard for retinal reattachment with a single procedure should be set in the region of 85% to 90%. Changing the model of care so that primary retinal reattachment surgery is predominantly performed by a specialist VRU has important resource implications.

Does Horner's syndrome in infancy require investigation?

AIMS: To evaluate whether isolated Horner's syndrome presenting in the first year of life warrants investigation. METHODS: Retrospective review of 23 children presenting with Horner's syndrome in the first year of life. RESULTS: In 16 patients (70%) no cause was identified. Birth trauma was the most common identifiable cause (four patients). Twenty one children (91%) had urinary vanillylmandelic acid (VMA) measured and 13 patients (57%) underwent either computed tomography or magnetic resonance imaging of the chest and neck. These investigations revealed previously undisclosed pathology in only two--one ganglioneuroma of the left pulmonary apex and one cervical neuroblastoma. A further patient was known to have abdominal neuroblastoma before presenting with Horner's syndrome. There were no cases of Horner's syndrome occurring after cardiothoracic surgery. Long term follow up of the patients (mean 9.3 years) has not revealed further pathology. CONCLUSIONS: Routine diagnostic imaging of isolated Horner's syndrome in infancy is unnecessary. Infants should be examined for cervical or abdominal masses and involvement of other cranial nerves. If the Horner's syndrome is truly isolated then urinary VMA levels and follow up in conjunction with a paediatrician should detect any cases associated with neuroblastoma. Further investigation is warranted if the Horner's syndrome is acquired or associated with other signs such as increasing heterochromia, a cervical mass, or cranial nerve palsies.

Improved genetic mapping of X linked retinoschisis.

X linked retinoschisis (RS) causes poor vision in affected males owing to radial cystic changes at the macula. Genetic linkage analysis was carried out in 16 British families with X linked retinoschisis using markers from the Xp22 region. Linkage was confirmed between the RS locus and the markers DXS207 (lod score, Zmax = 17.9 at recombination fraction theta = 0.03; confidence interval for theta = 0.007-0.09), DXS1053 (Zmax = 18.0 at theta = 0.01, CI = 0.001-0.06), DXS43 (Zmax = 12.9 at theta = 0.03, CI = 0.004-0.09), DXS1195 (Zmax = 6.4 at theta = 0.00), DXS418 (Zmax = 8.2 at theta = 0.00), DXS999 (Zmax = 21.2 at theta = 0.01, CI = 0.001-0.05), DXS443 (Zmax = 14.2 at theta = 0.03, CI = 0.004-0.09), DXS365 (Zmax = 24.5 at theta = 0.008, CI = 0.001-0.04). Key recombinants placed RS between DXS43 distally and DXS999 proximally. Multipoint linkage analysis gave odds of 344:1 in favour of this location for RS and supported the map Xpter-(DXS207, DXS1053)-DXS43-1 cM-RS-1 cM-DXS999-DXS443-DXS365-DXS1052-Xcen.

Clinical features in affected males with X-linked retinoschisis.

OBJECTIVES: To assess the phenotypic variation and visual prognosis of affected males with X-linked retinoschisis. DESIGN: Patients were ascertained from clinical geneticists and ophthalmologists in the United Kingdom. Genetic linkage analysis was carried out using polymorphic microsatellite markers from the Xp22 region of the X chromosome. PATIENTS: Fifty-six males from 16 British families with X-linked retinoschisis. RESULTS: Best-corrected visual acuity ranged from 20/20 to 20/600; 14 (25%) of the patients saw 20/40 or better, and 27 (55%) read N6 or better. Visual acuity was poorer in older patients (chi 2 =30.4, df=4, P<.001). Macular abnormalities were seen in all eyes. Foveal schisis was the most common abnormality seen in patients younger than 40 years (73 eyes [83%]), but in older patients a blunted foveal reflex or pigmentary atrophy was more common (17 eyes [85%]). Peripheral retinoschisis was seen in 40 (71%) of the patients. Vitreous hemorrhage occurred in 12 (21%) and retinal detachment in nine (16%) of the patients. Four eyes were blind as a result of retinal detachment. CONCLUSIONS: Although no evidence exists for genetic heterogeneity in X- linked retinoschisis, there is wide phenotypic variation. The most serious sight-threatening complications are vitreous hemorrhage and retinal detachment. In uncomplicated cases, the prognosis for vision is good, although deterioration of vision occurs in the fourth and fifth decades of life because of macular atrophy.

Infantile presentation of X linked retinoschisis.

Five infants who presented with nystagmus and/or strabismus were found to have bilateral highly elevated bullous retinoschisis involving the macula. Haemorrhage was present within the schisis cavity or the vitreous in four patients. The bullous retinoschisis eventually reattached spontaneously leaving pigment demarcation lines. A family history of X linked retinoschisis (XLRS) was known in two of the patients but in the other three subsequent investigation showed other male family members to be affected. It is important to recognise this uncommon presentation of XLRS so that the correct diagnosis is made and appropriate genetic counselling is given. Surgical treatment is not usually indicated and the visual prognosis is better than the initial appearance may suggest.

Extracapsular cataract surgery with lens implantation in diabetics with and without proliferative retinopathy.

In a retrospective study we have examined all diabetics (66 operated eyes) and an equal number of non-diabetic matched controls who underwent extracapsular cataract extracation (ECCE) with intraocular lens (IOL) implantation over a two-year period ending in December 1987. Of the diabetic patients' 76% eyes improved by at least two lines of Snellen acuity postoperatively. Of these patients 68% eyes and of the control eyes 83% achieved an acuity of 6/12 or better. In the diabetics the visual outcome depended on the state of the retinopathy and in particular the maculopathy. The diabetic group had a greater incidence of postoperative inflammation, but the major complications were related to continuing neovascularisation. Early postoperative laser photocoagulation may help to prevent these proliferative complications, and, provided a large, adequate capsulotomy is performed for capsular thickening, the presence of an IOL does not interfere with this photocoagulation. We also advise early postoperative assessment, and treatment if necessary, of any maculopathy. Diabetic retinopathy should no longer be regarded as a contraindication to intraocular lens insertion.