Whole exome sequencing of 491 individuals with inherited retinal diseases reveals a large spectrum of variants and identification of novel candidate genes.

BACKGROUND: Inherited retinal diseases (IRDs) include a range of vision loss conditions caused by variants in different genes. The clinical and genetic heterogeneity make identification of the genetic cause challenging. Here, a cohort of 491 unsolved cases from our cohort of Israeli and Palestinian families with IRDs underwent whole exome sequencing (WES), including detection of CNVs as well as single nucleotide variants (SNVs). METHODS: All participants underwent clinical examinations. Following WES on DNA samples by 3 billion, initial SNV analysis was performed by 3 billion and SNV and CNV analysis by Franklin Genoox. The CNVs indicated by the programme were confirmed by PCR followed by gel electrophoresis. RESULTS: WES of 491 IRD cases revealed the genetic cause of disease in 51% of cases, of which 11% were due wholly or in part to CNVs. In two cases, we clarified previously incorrect or unclear clinical diagnoses. This analysis also identified ESRRB and DNM1 as potential novel genes. CONCLUSION: This analysis is the most extensive one to include CNVs to examine IRD causing genes in the Israeli and Palestinian populations. It has allowed us to identify the causative variant of many patients with IRDs including ones with unclear diagnoses and potential novel genes.

Genetics of bilateral pediatric cataract in the Israeli and Palestinian populations.

PURPOSE: Bilateral pediatric cataract (BPC) is one of the most common causes of childhood visual impairment and blindness worldwide. A significant percentage of pediatric cataracts are caused by genetic alterations. We aim to characterize the set of genes and variants that cause BPC in the Israeli and Palestinian populations and to assess genotype-phenotype correlation. METHODS: Retrospective study in a multidisciplinary center for visual impairment, located in a tertiary medical center. Medical charts of families who underwent genetic counseling because of BPC in a family member were reviewed. Clinical characteristics and genetic tests results were obtained from medical records of affected subjects. RESULTS: Twenty-two families (47 patients) underwent genetic counseling and completed genetic testing. Causative variants were identified in 18/22 (81.8%) of the families, including 3 novel variants. Genetic testing used included mainly panel for congenital cataracts and whole exome sequencing. Eleven families performed genetic testing with the intention of future pregnancy planning. Main causative genes identified were crystalline genes followed by transcription factor genes. BCOR gene variants were associated with persistent fetal vasculature (PFV) cataract in two of three families. CONCLUSIONS: Combined molecular techniques are useful in identifying variants causing pediatric cataracts and showed a high detection rate in our population. BCOR gene variants might be associated with PFV type of cataracts. The study of pathogenic variants may aid in family planning and prevention of pediatric cataracts in future pregnancies. Additionally, in certain cases, it assists in diagnosing non-suspected syndromic types of pediatric cataracts.

Mild aniridia phenotype: an under-recognized diagnosis of a severe inherited ocular disease.

PURPOSE: Aniridia is a rare panocular disorder caused by mutations in the PAX6 gene and characterized mainly by iris hypoplasia. Here, we present six families with a history of low vision/blindness with a previously undiagnosed mild aniridia phenotype with minimal iris changes. METHODS: Retrospective case series of patients diagnosed with a subtle aniridia phenotype characterized by minimal iris abnormalities, foveal hypoplasia, and an identified mutation in PAX6. Data collection from patient's charts included ocular examination findings, visual acuity, refraction, and clinical pictures when available. Genetic analysis was performed by isolation of genomic DNA from peripheral blood. The main outcome was the identification of patients with mild aniridia harboring a PAX6 mutation. RESULTS: In all six families, the phenotype included minimal corectopia and foveal hypoplasia; nystagmus was present in 10 out of 11 patients. A PAX6 mutation was identified in all six families; three of these mutations were identified previously, and three are novel mutations. All the mutations are located within the conventional 128-residue paired domain of PAX6. CONCLUSIONS: A mild form of aniridia should be considered in the differential diagnosis of patients with low vision associated with mild iris abnormalities, nystagmus, and foveal hypoplasia. To ensure an accurate diagnosis of aniridia, minimal pupillary changes and/or incipient keratopathy should be examined. The broad phenotypic heterogeneity among aniridia leads to the fact that eye care clinicians must have a high index of suspicion for the disease when seeing undiagnosed low vision patients, because proper diagnosis can improve management as well as facilitate genetic testing and counselling.

Visual acuity improvement in children with albinism beyond the first decade of life.

PURPOSE: To determine if visual maturation continues beyond the first decade of life in children with albinism and whether this is related to albinism type, presence of nystagmus, eye muscle surgery or refractive errors. DESIGN: Case series based on retrospective study of children with confirmed genetic diagnosis of albinism. METHODS: Clinical data were obtained from medical files of children examined during school years, including albinism type, visual acuity, eye muscle surgery, nystagmus, and others on different visits (Visit 1: ages 7-9; Visit 2: ages: 10-12; Visit 3: ages 13-16; Visit 4: ages >16). RESULTS: Seventy-five children with albinism were included in the study. Patients were divided into different groups according to the albinism type including OCA1A: 17; OCA1B: 28; OCA2: 26; HPS: 3; OCA4: 1. Follow-up ranged from 3-13 years. Progressive visual acuity improvement was seen in all three main groups. T-test paired samples showed a statistically significant improvement when comparing vision from Visit 1 and Visit 3 in both OCA1A and OCA2 groups, with a mean vision improvement of 2 lines. There was no correlation between visual improvement and refractive error, eye muscle surgery or nystagmus. CONCLUSION: An improved visual performance was seen in a large percentage of children with albinism during the second decade of life. The reason for this late improvement in vision is not clear but may be related to late foveal maturation or improvement in nystagmus with time. This information is useful for clinicians of these patients and when counseling parents.

The prevalence of autism among children with albinism.

BACKGROUND: The association between Autism spectrum disorders (ASD) and visual impairment has been mentioned in the literature. The aim of our study was to investigate the prevalence of autism among children with albinism compared to the prevalence of ASD in children with visual impairment secondary to other causes. METHODS: Retrospective study of children with albinism from January 2015 to December 2020. A control group was created with children with early onset visual impairment of similar visual range and age, secondary to diagnosis other than albinism. Patients with associated Autism were identified in both groups. RESULTS: Seven hundred and eight children aged 1-18 years with visual impairment were included in the study. 401 children had a diagnosis of albinism, of whom 14 were also diagnosed with ASD. In the control group, composed of 307 patients, only 3 had ASD (p: 0·03). CONCLUSIONS: The prevalence of ASD in patients with albinism was 1 in 28, while in children with visual impairment from other causes was 1 in 102. We aim to raise awareness of the higher prevalence of autism in children diagnosed with albinism in order to reach earlier diagnosis and support.

Childhood visual impairment and blindness: 5-year data from a tertiary low vision center in Israel.

BACKGROUND: To assess the main causes leading to childhood visual impairment/blindness in a center for low vision in Israel and to analyze the literature on pediatric blinding diseases in developed countries. METHODS: Retrospective study based on observational case series. Data were obtained from medical records of visually impaired children, seen at a national referral low vision center. Children were divided into two groups: moderate visual impairment (6/18 to 6/60) and severe visual impairment (SVI)/blindness (<6/60). Inherited eye diseases (IED) were grouped together for analysis. Data from the Israeli blind registry from the same period of time were analyzed for comparison. A review of literature on childhood blindness in developed countries since 2000 was conducted. RESULTS: A total of 1393 children aged 0-18 years were included in the study. Moderate visual impairment was seen in 1025 (73.6%) and SVI/blindness in 368 (26.4%) of the studied children. Among blind children, IED accounted for at least 51% of all diagnoses, including mainly albinism and retinal dystrophies. IED prevalence was equally high in both main ethnic groups (Jewish and Arab Muslims). Non-IED (22.6%) included mainly patients with cerebral visual impairment and retinopathy of prematurity. CONCLUSIONS: The leading cause of childhood visual impairment and blindness in our patient cohort was IED. Analyses of the literature from the last two decades show that IED are a major cause for SVI/childhood blindness in other developed countries as well. Updated patterns of global childhood blindness may suggest a need for new approach for screening programs and modern tactics for prevention.

Prevalence and associated factors of cystoid macular edema in children with early onset inherited retinal dystrophies.

PURPOSE: To assess the prevalence of Cystoid macular edema (CME) in children with early onset retinal dystrophies (EORD) and to evaluate if there are associated factors and/or response to early treatment. METHODS: Consecutive, retrospective case series. Medical records of patients, 18 years or younger, diagnosed with EORD were included in the study. Optic coherence tomography (OCT) scans, clinical and genetic characteristics as well as other associated factors were analyzed. Main outcome was the presence of CME on OCT scans. RESULTS: One hundred and two children with EORD (aged 1-18 years, mean 9.7 ± 4.2) were recruited. OCT was performed in 60/102 and among them, 19/60 had CME (31.7%). The disease-causing gene was identified in 13 children with CME; autosomal-recessive inheritance was found in 88.3% of those with an identified genotype. Children with Usher syndrome had CME in 44.4% of the cases. Early treatment of CME resulted in variable response. CONCLUSIONS: Our results show that 31.7% of children with EORD who underwent OCT have macular edema. CME prevalence was found to be relatively higher in children with Usher syndrome. Autosomal recessive was the most prevalent inheritance identified in the EORD group as well as in the CME group. Additional prospective research is needed to assess the efficacy of early CME treatment in pediatric EORD patients.

Variable phenotype of Knobloch syndrome due to biallelic COL18A1 mutations in children.

PURPOSE: Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele. Our aim is to report the clinical and genetic findings of four Israeli children affected by Knobloch syndrome. METHODS: Retrospective study of four patients diagnosed with Knobloch syndrome, who underwent full ophthalmic examination, electroretinography, and neuroradiologic imaging. Genetic analysis included whole exome sequencing (WES) and Sanger sequencing. RESULTS: The four patients included in this study had high myopia and nystagmus at presentation. Ocular findings included vitreous syneresis, macular atrophy, macular coloboma, and retinal detachment. One child had iris transillumination defects and an albinotic fundus, initially leading to an erroneous clinical diagnosis of albinism. Electroretinography revealed a marked cone-rod pattern of dysfunction in all four children. Brain imaging demonstrated none to severe occipital pathology. Cutaneous scalp changes were present in three patients. WES analysis, confirmed by Sanger sequencing revealed COL18A1 biallelic null mutations in all affected individuals, consistent with autosomal recessive inheritance. CONCLUSIONS: This report describes variable features in patients with Knobloch syndrome, including marked lack of eye pigment similar to albinism in one child, macular coloboma in two children as well as advanced cone-rod dysfunction in all children. One patient had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of this syndrome, with its variable phenotype may aid early diagnosis, monitoring for potential complications, and providing appropriate genetic counseling.

A Novel Method of Video Recording Ophthalmic Surgical Procedures.

BACKGROUND: Modern surgical microscopes are equipped with video recording and broadcasting capability. We present a simple method for utilizing these systems even in circumstances where the surgeon is operating with surgical loupes. METHODS: A divergent lens is suspended immediately below the objective of the microscope, thereby increasing the microscope's working distance. The microscope can be suspended high above the patient, out of the surgeon's field of view, yet still provide excellent video recording of the surgical procedure. RESULTS: The technique has been used successfully in over 30 surgical cases. CONCLUSION: This method offers a simple solution for recording surgical procedures that do not use the operating microscope. The implications are relevant to surgeons who operate with surgical loupes.

Uveal melanoma in Israel in the last two decades: characterization, treatment and prognosis.

BACKGROUND: Uveal melanoma is the most common primary intraocular tumor in adults. In the last two decades the Hadassah-Hebrew University Medical Center ocular oncology clinic has become a referral center for uveal melanoma patients. OBJECTIVES: To describe the characteristics of uveal melanoma patients in Israel, their treatment modalities and outcomes during the years 1988-2007. METHODS: Data were collected from the files of uveal melanoma patients in the departments of ophthalmology and oncology in our facility. Statistical analysis was performed using JMP statistical software. RESULTS: Data were available for 558 patients. The annual incidence of uveal melanoma in the last 5 years was 47.2 +/- 7.1 new cases per year (mean +/- standard error). There were 309 women (55.4%). The age at diagnosis was 60.8 +/- 16.5 years (range 5-95). Overall, 6.6%, 16.8% and 86.9% involved the iris, ciliary-body and choroid, respectively. Tumors were classified as small, medium and large (9.0%, 64.5% and 17.9%, respectively) according to the COMS grouping criteria. The most common primary treatment was brachytherapy (74%), followed by enucleation (17.9%). Local recurrence was noted in 11.1% of patients, while metastases developed in 13.3%. The 5, 10 and 15 year melanoma-related mortality rate was 11.4%, 17.0% and 23.3%, respectively. Of the overall study population 9.3% died of metastatic uveal melanoma. CONCLUSIONS: Uveal melanoma patients in Israel have tumors with characteristics similar to those in other countries. Brachytherapy is the predominant treatment, the local recurrence rate is low, and survival is comparable to that reported in the medical literature.

Graded Anderson procedure for correcting abnormal head posture in infantile nystagmus.

PURPOSE: To describe the long-term results of Anderson procedure, which includes recession of the two extraocular yoke muscles responsible for eccentric eye position and abnormal head posture (AHP) in patients with infantile nystagmus. METHODS: Retrospective data collection of patients who underwent an Anderson procedure at a single medical center by one surgeon from 2008 to 2016. The main outcome measure was the elimination of AHP following surgery. RESULTS: Twenty-seven patients (18 males, 9 females) underwent an Anderson procedure during the study period. The average age at surgery was 8.6 ± 7.7 years and mean follow-up was 3.5 ± 2.4 years (range, 6 months-9 years). Before surgery all patients had AHP (17 left and 10 right head turns) greater than 25° (mean 40.1 ± 6.7°) that decreased significantly following surgery (mean 7.2 ± 7.6°, P < 0.001). Surgery resulted in complete elimination of AHP in 14 (52%) patients. In 10 (37%) patients the residual head turn was 15° or lower, and in only 3 (8%) the post-operative AHP was 25° or larger, requiring further surgery. It is important to note that none of the patients developed strabismus or duction limitation following surgery. CONCLUSIONS: Long-term results following the Anderson procedure show a stable decrease in AHP in patients with infantile nystagmus, often resulting in complete restoration of normal head posture. Involved risks of strabismus and limitation of ocular motility appear to be low.

TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations.

Precise genetic and phenotypic characterization of congenital stationary night blindness (CSNB) patients is needed for future therapeutic interventions. The aim of this study was to estimate the prevalence of CSNB in our populations and to study clinical and genetic aspects of the autosomal recessive (AR) form of CSNB. This is a retrospective cohort study of Palestinian and Israeli CSNB patients harboring mutations in TRPM1 underwent comprehensive ocular examination. Genetic analysis was performed using homozygosity mapping and sequencing. 161 patients (from 76 families) were recruited for this study, leading to a prevalence of 1:6210 in the vicinity of Jerusalem, much higher than the worldwide prevalence. 61% of the families were consanguineous with AR inheritance pattern. Biallelic pathogenic TRPM1 mutations were identified in 36 families (72 patients). Two founder mutations explain the vast majority of cases: a nonsense mutation c.880A>T (p.Lys294*) identified in 22 Palestinian families and a large genomic deletion (36,445 bp) encompassing exons 2-7 of TRPM1 present in 13 Ashkenazi Jewish families. Most patients were myopic (with mean BCVA of 0.40 LogMAR) and all had absent rod responses in full field electroretinography. To the best of our knowledge, this is the largest report of a clinical and genetic analysis of patients affected with CSNB due to TRPM1 mutations.

Implementing enhanced education to improve the UCLA Preschool Vision Program.

PURPOSE: To examine whether educational pamphlets and videos for adults can increase follow-up rates for eye examinations among preschool children. METHODS: The target population was 3- to 5-year-olds attending preschools within Los Angeles County and receiving services from the UCLA Preschool Vision Program (UPVP). Preschools were randomly assigned to standard and enhanced-education groups. The same procedures were followed in each group, except that preschool personnel and parents of children referred for eye examinations in the enhanced-education group received education materials and watched a 3-minute informational video on the screening day. The outcome measure was the follow-up rate for comprehensive examinations performed by the UPVP on a second date. RESULTS: The follow-up rate for receiving a complete eye examination was 75.3% (438/582) in the enhanced-education group and 65.1% (430/661) in the standard group (P < 0.0001 [Fisher exact test]; OR = 1.63; 95% CI, 1.28-2.09). CONCLUSIONS: Educating adults during the screening session can increase follow-up rates. Further studies are recommended to understand barriers to seeking eye care for children and to devise initiatives to help increase targeted awareness.

Long-term uveal melanoma survivors: measuring their quality of life.

PURPOSE: Patients with uveal melanoma (UM) undergo lifelong follow-up as metastases can occur more than 20 years after diagnosis. Little is known about the quality of life (QoL) of UM survivors over such an extended period. To investigate their QoL, we used various estimating factors. METHODS: A cohort of patients diagnosed and treated for UM with regularly scheduled follow-up visits was asked to fill in a European Organization for Research and Treatment of Cancer (EORTC) questionnaire comprised of the EORTC QLQ-C30 and EORTC QLQ-OPT30 modules. An additional open question examined other changes in the patients' lifestyle since diagnosis. Independent demographic and medical data were collected from patient records. RESULTS: Two hundred and thirty-two of 294 patients agreed to complete the questionnaire. General QoL correlated highly with the eye-related QoL. Statistically significant higher QoL was associated with tumours not involving the ciliary body, and with better best-corrected visual acuity (BCVA). A subgroup of 39% of the patients reported severe disability affecting eye-related tasks. Thirty-three per cent were highly concerned about various aspects of their future health. Patients who underwent enucleation reported lower eye-related QoL and described problems related to body image in response to the open question. CONCLUSION: General QoL of UM patients is only slightly affected by their malignancy. However, body image and psychosocial adjustment are major issues involved in evaluating QoL. Continuous long-term psychosocial treatment is needed from the time of diagnosis in a subgroup of patients suffering from eye-related disabilities.

The UCLA preschool vision program, 2012-2013.

PURPOSE: To introduce the University of California Los Angeles (UCLA) Preschool Vision Program (UPVP) and describe the utilization pattern and challenges of the first year of implementation. METHODS: The UPVP aims to improve vision in 3- to 5-year-old preschoolers of Los Angeles County. On the first visit, trained personnel use a handheld autorefractometer (Retinomax 3; Righton, Japan) for initial screening and identify those who would benefit from a complete eye examination. On the second visit, the UCLA Mobile Eye Clinic staff and ophthalmologists provide follow-up examinations. Prescribed eyeglasses are fit and provided by program personnel on the school site on a separate visit. Follow-up calls are made to ensure compliance. RESULTS: From a population of 12,088 children in 215 preschools, 11,260 preschoolers (mean age, 4.3 years; 49.2% females) were screened successfully. In this sample, 86% were Latino, and almost all (97%) spoke either Spanish or English. About 65% of referred preschoolers underwent a complete eye examination. Prescription eye glasses were provided for 850 preschoolers (7.5%); 95 children (0.8%) were newly diagnosed with amblyopia. CONCLUSIONS: A large proportion of Los Angeles County preschoolers with refractive errors have unmet needs in terms of refractive correction. Further studies are recommended to understand barriers to eye care for children and to devise initiatives for Los Angeles's large, densely populated, and complex community to increase awareness and willingness.

Refractive Errors and Amblyopia in the UCLA Preschool Vision Program; First Year Results.

PURPOSE: To report the outcomes of full ophthalmic examination for preschool children in LA County who failed screening with the Retinomax Autorefractor. DESIGN: Retrospective, cross-sectional study. METHODS: Between August 2012 and May 2013, the University of California Los Angeles (UCLA) preschool vision program screened 11 260 preschool children aged 3-5 years in Los Angeles County using the Retinomax Autorefractor only. Of those, 1007 children who failed the screening were examined by an ophthalmologist on the UCLA Mobile Eye Clinic. Data from the eye examination were recorded for all children. Amblyopia was defined as unilateral if there was ≥2 line interocular difference in the best-corrected visual acuity (BCVA) and as bilateral if BCVA was <20/50 for children <4 years old and <20/40 for children ≥4 years old. RESULTS: Glasses were prescribed for 740 (74%) of those examined. Uncorrected visual acuity for all examined children was 0.4 ± 0.2 (logMAR mean ± SD), and BCVA was 0.2 ± 0.1. Of the 88% who underwent cycloplegia, 58% had hyperopia (spherical equivalent [SE] ≥+0.50 diopter [D]), mean of +2.50 D, and 21% had myopia (SE ≤-0.50 D), mean of -1.40 D. A total of 69% had astigmatism ≥1.50 D, mean of 1.97 D (range 0-5.75). Spherical and cylindrical anisometropia ≥1.00 D were each found in 26% of those examined. Refractive amblyopia was found in 9% of those examined, or 0.8% of the original population. Of the amblyopic subjects, 77% were unilateral. CONCLUSIONS: Screening of preschoolers with the Retinomax led to diagnosis and early treatment of uncorrected refractive errors and amblyopia. By treating children early, amblyopia may be prevented, quality of life improved, and academic achievements enhanced.

Adjustable augmented rectus muscle transposition surgery with or without ciliary vessel sparing for abduction deficiencies.

BACKGROUND: Vertical rectus transposition (VRT) is useful in abduction deficiencies. Posterior fixation sutures enhance the effect of VRT, but usually preclude the use of adjustable sutures. Augmentation of VRT by resection of the transposed muscles allows for an adjustable technique that can reduce induced vertical deviations and overcorrections. METHODS: We retrospectively reviewed the records of all patients undergoing adjustable partial or full tendon VRT augmented by resection of the transposed muscles. Ciliary vessels were preserved in most of the patients by either splitting the transposed muscle or by dragging the transposed muscle without disrupting the muscle insertion. RESULTS: Seven patients with abducens palsy and one with esotropic Duane syndrome were included. Both vertical rectus muscles were symmetrically resected by 3-5 mm. Preoperative central gaze esotropia of 30.6 ± 12.9Δ (range, 17-50Δ) decreased to 10.6 ± 8.8Δ (range, 0-25Δ) at the final visit (p = 0.003). Three patients required postoperative adjustment by recession of one of the transposed muscles due to an induced vertical deviation (mean 9.3Δ reduced to 0Δ), coupled with overcorrection (mean exotropia 11.3Δ reduced to 0 in two patients and exophoria 2Δ in one patient). At the final follow-up visit 3.8 ± 2.6 months postoperatively, one patient had a vertical deviation <4Δ, and none had overcorrection or anterior segment ischemia. Three patients required further surgery for recurrent esotropia. CONCLUSIONS: Augmentation of VRT by resection of the transposed muscles can be performed with adjustable sutures and vessel-sparing technique. This allows for postoperative control of overcorrections and induced vertical deviations as well as less risk of anterior segment ischemia.

Does inferior oblique recession cause overcorrections in laterally incomitant small hypertropias due to superior oblique palsy?

AIM: To evaluate the effects of inferior oblique muscle recession (IOR) in cases of laterally incomitant hypertropia <10 prism dioptres (PD) in central gaze thact 2t are clinically consistent with superior oblique palsy (SOP). METHODS: We retrospectively reviewed patients with SOP and hypertropias <10 PD in central gaze who underwent graded IOR. Primary outcomes were reduction of lateral incomitance and number of overcorrections in central gaze. RESULTS: Twenty-five patients were included. Mean follow-up was 13.8 months (range 1.4-66). Mean central gaze hypertropia decreased from 5.6±2.1 to 0.2±1.6 PD (p<0.001). Contralateral gaze hypertropia decreased from 15.9±7.6 to 2.3±3.3 PD (p<0.001). Lateral incomitance (central vs contralateral gaze) was 10.3±6.9 PD preoperatively and 2.0±3.0 PD postoperatively (p<0.001). There were two patients overcorrected in central gaze, and one patient overcorrected in downgaze. One patient necessitated further surgery for overcorrection. CONCLUSIONS: Although small hypertropias can be treated with prisms or small, adjustable inferior rectus recessions, IOR collapses incomitance without causing much overcorrection. IOR is a reasonable treatment for small, laterally incomitant hypertropia due to SOP.

Isolated y-splitting and recession of the lateral rectus muscle in patients with exo-duane syndrome.

PURPOSE: Weakening of both horizontal rectus muscles is performed for patients with Duane syndrome and significant misinnervation of the lateral rectus (LR) muscle resulting in strabismus, limitation to ocular rotations, and globe retraction. In patients with severe up-/downshoots, a Y-splitting of the LR is often recommended. The purpose of this study was to evaluate the efficacy of isolated unilateral LR recession-Y splitting in exo-Duane patients with limitation to adduction and up-/downshoots. METHODS: etrospective review of the records of consecutive patients with exo-Duane syndrome and up/down-shoots who underwent isolated Y-splitting-recession of the affected LR. RESULTS: The records of 10 patients were reviewed (mean age at surgery 23 ± 21 years). The Y-split was performed 10 mm posterior to the insertion and was combined with a mean LR recession of 8.7 ± 2.9 mm. Torticollis decreased from 12.7 ± 4.4° to 4.8 ± 5.3° (P = 0.003). Exotropia improved from 18.4 ± 7.3 to 6.2 ± 5.9 PD postoperatively (P < 0.001). Exotropia in contralateral gaze improved from 33.7 ± 11.8 to 18.7 ± 18.1 PD postoperatively (P = 0.09). No significant postoperative changes in esotropia in ipsilateral gaze, vertical deviations, or ocular rotations in adduction or abduction were observed. Downshoots were significantly decreased (P = 0.01), and there was a trend toward improvement of upshoots (P = 0.07). There were no overcorrections, although 3 patients required additional LR weakening and transposition. CONCLUSIONS: LR Y-splitting-recession improves ocular alignment, torticollis, and up-/downshoots. LR recession improves ocular alignment and torticollis, while the addition of a Y-split procedure improves up-/downshoots.

Trends in liver function tests: a comparison with serum tumor markers in metastatic uveal melanoma (part 2).

AIM: To compare trends in liver function test (LFT) levels over consecutive visits before detection of liver metastasis (LM) from uveal melanoma (UM) with such trends in the serum tumor markers S-100ß, melanoma inhibitory activity (MIA), osteopontin (OPN), and tissue polypeptide-specific antigen (TPS). PATIENTS AND METHODS: Blood was drawn from 32 patients with metastatic UM and 43 disease-free (DF) patients semi-annually for levels of S-100ß, MIA, OPN, and TPS. Abdominal ultrasonography (US) and LFTs were used to detect LM. Median LFT levels were calculated at 6-month intervals prior to the clinical detection of LM. Trends in LFT levels over consecutive visits in the groups were compared with trends in the tumor markers for these groups. RESULTS: Only LDH gave a statistically significant difference between the trends of the metastasis and DF groups (p=0.0041). When calculating the lead time, all of the elevations were non-significant except for gamma glutamyltransferase which showed a statistically significant elevation at time 0, the time of detection of metastasis. LDH showed a rise at 0-6 months before detection, but this was not significant. For the tumor markers, steeper trendlines were shown for the metastasis group for MIA and S-100ß, and most of the markers showed a lead time of more than six months, although this was statistically significant only for OPN. CONCLUSION: Following the dynamics of tumor markers and LFTs may help to find metastatic disease in UM patients before the metastases are detectable by imaging, enabling earlier treatment.