Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases.

BACKGROUND: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. METHODS: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. RESULTS: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. CONCLUSION: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

Clinical course of two siblings with potassium voltage-gated channel modifier subfamily V member 2 (KCNV2)-associated retinopathy.

BACKGROUND: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR. CASE REPORTS: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene. CONCLUSIONS: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR.

Fundus autofluorescence, optical coherence tomography and electroretinography abnormalities in a patient with digoxin retinopathy that resemble those in KCNV2-associated retinopathy.

BACKGROUND: Digoxin related retinal toxicity causes blurred vision, photophobia, central scotoma, color vision abnormality, and electroretinography (ERG) abnormalities. Here, we report a case with transient abnormalities in vison, in which fundus autofluorescence (FAF), optical coherence tomography (OCT), and ERG findings resembled those in KCNV2 (potassium voltage-gated channel modifier subfamily V member 2)-associated retinopathy. CASE REPORT: An 89-year-old woman presented with complaints of acute blurred vision, nyctalopia, photophobia, and color vision abnormality. She received digoxin for tachycardia induced by atrial fibrillation for a month. The fundi showed a faint white ring at the fovea, which showed hyperfluorescence in FAF. OCT showed a thickened EZ in the macula. A dark-adapted (DA)-30 ERG showed a reduced and "squaring (trough-flattened)" a-wave, and a delayed, supernormal b-wave, resulting in a high b/a-wave amplitude ratio. The digoxin dose was reduced following an elevation in serum levels. Five weeks later, her visual acuities improved, and abnormal hyperfluorescence on FAF disappeared. After 6 months, no visual symptoms were reported. The ellipsoid-zone thickening in OCT improved; however, the b/a-wave amplitude ratio on DA-30 ERG remained high. The b-wave in LA-long-flash ERG was initially reduced, which improved after correction of serum level of digoxin. CONCLUSIONS: The patient's clinical findings resembled those of patients with KCNV2-associated retinopathy or temporal hyperkalemia. These disorders appear to have a common pathogenesis, which may be related to abnormal extracellular potassium levels in the retina. The on-bipolar cells seemed to be more affected than the off-bipolar cells in digoxin related retinal toxicity.

EFFICACY OF INNER WALL RETINECTOMY FOR BULLOUS SCHISIS CAVITY HANGING OVER OR THREATENING THE MACULA IN PATIENTS WITH CONGENITAL X-LINKED RETINOSCHISIS.

PURPOSE: To present the clinical characteristics, surgical outcomes, and surgical complications of patients with congenital X-linked retinoschisis who underwent vitrectomy for bullous schisis cavity hanging over or threatening the macula. METHODS: Nine patients with congenital X-linked retinoschisis (12 eyes) who underwent vitrectomy at three tertiary hospitals and completed ≥3 years of postoperative follow-up were retrospectively investigated. Data were collected from patients' charts, including age at vitrectomy, surgical procedures, and postoperative complications. RESULTS: The age at vitrectomy ranged 4 months to 103 months (median: 14 months). Inner wall retinectomy was performed during the initial vitrectomy in eight eyes. Among the eight eyes that initially underwent inner wall retinectomy, one (12.5%) required subsequent retinal surgery for postoperative complication. Furthermore, four eyes did not undergo initial inner wall retinectomy but required subsequent retinal surgeries for postoperative complications. Three of five eyes (60.0%) treated with silicone oil tamponade and two of seven eyes (28.6%) that were not treated with silicone oil tamponade during the initial vitrectomy required subsequent retinal surgeries for postoperative complications. All eyes maintained a clear central visual axis at the last examination. CONCLUSION: Inner wall retinectomy seems beneficial in achieving a clear visual axis in eyes with bullous schisis cavity hanging over or threatening the macula in patients with congenital X-linked retinoschisis.

Long-Term Visual Prognosis of Patients Following Lens-Sparing Vitrectomy for Stage 4A Retinopathy of Prematurity.

This study evaluated the long-term visual outcomes of patients in whom at least one eye underwent successful lens-sparing vitrectomy (LSV) for stage 4A retinopathy of prematurity (ROP). A retrospective chart review was conducted using the data of 61 eyes of 42 patients with a minimum 4-year follow-up after successful LSV, with or without anti-vascular endothelial growth factor (VEGF) therapy, and whose best-corrected visual acuity (BCVA) was measurable using Landolt rings at the final visit. The mean age at the final follow-up was 10.1 ± 3.3 years. Before LSV, all eyes underwent laser ablation therapy. Twenty eyes (32.8%) with high vascular activity received anti-VEGF therapy before LSV. The mean decimal BCVA at the final follow-up was 0.23 ± 0.26 (range: hand motion to 1.2). Twenty-three eyes (54.1%) had a decimal BCVA of ≥0.4. Among 49 phakic eyes at the final examination, the mean refractive error was -10.1 ± 5.0 D, with 37 eyes (75.5%) having high myopia (>-6.0 D). No significant differences were observed in terms of decimal BCVA and refractive errors between eyes with and without anti-VEGF therapy. Approximately half of the patients had a decimal BCVA of ≥0.4, despite myopic refraction after successful LSV for stage 4A ROP. LSV for stage 4A ROP seemed to be associated with good visual function, despite myopic refraction.

Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing.

Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.

STRUCTURAL OUTCOME AFTER SURGERY FOR STAGE 5 RETINOPATHY OF PREMATURITY BASED ON THE NEW INTERNATIONAL CLASSIFICATION: ICROP 3.

PURPOSE: This study investigated the outcomes of vitrectomy for Stage 5 retinopathy of prematurity (ROP) based on the International Classification of Retinopathy of Prematurity third edition, in which Stage 5 ROP is divided into three subgroups. METHODS: Fifty-four eyes of 34 patients with Stage 5 ROP who underwent vitrectomy between 2004 and 2020 were retrospectively analyzed. Data including sex, gestational age and weight at birth, International Classification of Retinopathy of Prematurity 3 subcategories, perioperative use of intravitreal bevacizumab injection and laser photocoagulation, surgical procedure and complications, final retinal reattachment, and follow-up period were collected. RESULTS: Complete retinal reattachment was achieved in 16 eyes (88.9%) with Stage 5A and 13 eyes (39.4%) with Stage 5B ( P = 0.0003, Wilcoxon rank-sum test). Three patients with Stage 5C were considered inoperable. Postoperative anatomical failure was significantly associated with stage (Stage 5B vs. 5A; odds ratio, 17.986; 95% confidence interval, 3.712-148.502; P = 0.0001, multivariate logistic regression analysis). Intraoperative intravitreal bevacizumab was significantly associated with lower postoperative incidence of vitreous hemorrhage and glaucoma ( P = 0.041, chi-square test). CONCLUSION: Staging of preoperative anatomical features based on International Classification of Retinopathy of Prematurity 3 is a useful predictor for final anatomical success. Intraoperative intravitreal bevacizumab might reduce postoperative complication risks.

Identification of Interphotoreceptor retinoid-binding protein in the Schisis cavity fluid of a patient with congenital X-linked Retinoschisis.

BACKGROUND: This case report describes the surgical outcome in a patient with congenital X-linked retinoschisis (CXLRS) and the results of proteomic analysis of surgically extracted samples from both vitreous and intraschisis cavities by mass spectrometry. CASE PRESENTATION: A 3-month-old boy presented with extensive retinoschisis involving macula and retinal periphery in both eyes. Genetic analysis confirmed retinoschisin 1 mutation (c.554C > T), and an electroretinogram showed significant reduction of b-wave and decreased cone and rod responses, which led to a diagnosis of CXLRS. By performing pars plana vitrectomy, including inner wall retinectomy, clear visual axes with stable retinal conditions and functional vision in both eyes were obtained during the 4 years of follow-up. Proteomic analysis of surgically retrieved fluid from the intraschisis cavity revealed a higher expression of interphotoreceptor retinoid-binding protein (IRBP) than that from the vitreous humor. However, both samples showed equal levels of albumin, transferrin, and pigment epithelium-derived factor. CONCLUSIONS: Cellular adhesive imperfection in CXLRS may cause IRBP diffusion from the interphotoreceptor matrix, resulting in the strong expression of IRBP in the intraschisis cavity. An impaired retinoid cycle caused by an absence of IRBP in the retina may potentially underlie the pathology of CXLRS.

The Effect of an Additional Core Suture During Pulvertaft Tendon Repair: A Fresh-Frozen Cadaver Study.

PURPOSE: Pulvertaft tendon repair is a strong suture technique; however, proper tendon tension is impaired by repair site elongation. Therefore, methods to reduce postoperative elongation are warranted. This study aimed to determine the effects of additional core sutures during Pulvertaft tendon repair on repair site elongation and rupture strength. METHODS: A total of 48 finger extensor tendons were harvested from fresh-frozen cadavers, and tendons with similar diameters were paired. The 24 pairs of tendons were divided into the following 4 groups: group I, 3 interlaced weaves only; group II, 3 interlaced weaves and 2 core suture strands with 4-0 nylon; group III, 3 interlaced weaves and 2 core suture strands with 4-0 FiberWire; and group IV, 4 interlaced weaves only. Each sutured tendon was placed in a Universal Testing Machine, and repair site elongation after repeated traction loads and rupture strength were measured. RESULTS: The mean elongation values were 2.74 ± 0.84 mm, 1.80 ± 0.16 mm, 1.60 ± 0.18 mm, and 1.92 ± 0.18 mm for groups I, II, III, and IV, respectively. The elongation values were significantly lower in groups II, III, and IV than in group I. The mean rupture strengths were 64.9 ± 16.0 N, 94.8 ± 17.2 N, 110.9 ± 21.3 N, and 104.9 ± 17.5 N for groups I, II, III, and IV, respectively. Rupture strengths were significantly higher for groups III and IV than for group I. CONCLUSIONS: After adding core sutures during Pulvertaft tendon repair, the elongation amount decreased, and the rupture strength improved. CLINICAL RELEVANCE: The study showed the effect of additional core sutures during Pulvertaft tendon repair, suggesting that it could be useful in reducing postoperative tendon elongation when extensor tendon transfers are performed.

FACTORS ASSOCIATED WITH REACTIVATION AFTER INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB THERAPY IN INFANTS WITH RETINOPATHY OF PREMATURITY.

PURPOSE: To investigate the efficacy and risk factors of intravitreal antivascular endothelial growth factor injection (anti-VEGF therapy) for retinopathy of prematurity (ROP). METHODS: We retrospectively reviewed 80 consecutive eyes of 43 patients with Type 1 ROP or worse who received anti-VEGF therapy during January 2012-February 2018. Patients were divided into those who were injected with 0.25 mg of bevacizumab (IVB group, 37 eyes) and 0.25 mg of ranibizumab (IVR group, 43 eyes). Serum VEGF concentrations of 18 patients were measured before and after IVR. RESULTS: Antivascular endothelial growth factor injection therapy reduced ROP activity in all eyes; however, 14 eyes (17.5%) exhibited reactivation. The reactivation rates of the IVB and IVR groups were 13.5% and 20.9%, respectively (P = 0.556). Multivariate logistic regression analysis showed that postmenstrual age ≤35 weeks at anti-VEGF therapy (P = 0.014) and aggressive posterior ROP (P = 0.044) was significantly associated with reactivation. Serum VEGF was significantly suppressed at Days 1 (P < 0.001) and 7 (P = 0.012) after IVR and returned to the preinjection level by Day 14 (P = 0.210). CONCLUSION: Both IVR and IVB seemed effective in reducing ROP activity. Reactivation after anti-VEGF therapy may be associated with younger postmenstrual age at anti-VEGF therapy and aggressive posterior ROP.

ULTRA-WIDE FIELD FUNDUS AUTOFLUORESCENCE IMAGING OF EYES WITH STICKLER SYNDROME.

PURPOSE: To determine the characteristics of fundus autofluorescence (FAF) images and visual functions in eyes with Stickler syndrome using ultra-widefield FAF images. METHODS: Forty-six eyes of 26 patients with mutations in the COL2A1 gene underwent ultra-widefield FAF imaging. The eyes were categorized into three types; no signs of abnormal AF, predominantly hyperfluorescent AF (hyper-AF), and predominantly hypofluorescent AF (hypo-AF). Goldmann perimetry was performed on 34 eyes, and line-scan images of the abnormal AF lesions were obtained by swept-source optical coherence tomography in 4 eyes. RESULTS: Abnormal AF lesions were found in 37 eyes of 21 (80.7%) of the 26 patients. Hyper-AF was found in 15 eyes and hypo-AF was found in 22 eyes. The FAF changes corresponded with the funduscopically observed radial paravascular retinal degeneration. The average age at the examination was significantly younger in patients who had eyes with hyper-AF or no abnormal AF than in those with hypo-AF (12.8 vs. 28.4 years; P = 0.009). Abnormal AF-associated visual field defects were found in 5/10 (50%) eyes with hyper-AF and 17/18 (94%) eyes with hypo-AF. Hyper-AF changes tended to appear before retinal changes were detectable by fluorescein angiography. An absence of the ellipsoid zone and the outer nuclear layer and a thinning of the overall retinal thickness were found corresponding to the hypo-AF lesions in the swept source optical coherence tomography images. CONCLUSION: Abnormal FAF is characteristic of eyes with Stickler syndrome. Age-related alterations of the FAF was associated with visual field defects and disruption of the photoreceptors and retinal pigment epithelial cells.

Complete Visual Recovery From Severe Outer Retinitis After Tonsillitis.

BACKGROUND: To report a case of severe acute bilateral outer retinitis after tonsillitis and rapid morphologic and functional recovery after steroid treatment. METHODS: Observational case report. RESULTS: A 26-year-old woman with acute bilateral blurred vision that developed after tonsillitis underwent spectral-domain optical coherence tomography (SD-OCT) that showed photoreceptor outer segment damage. Full-field electroretinography (ERG) and multifocal ERG were nonrecordable. The patient had a remarkable anatomic and functional recovery in response to steroid treatment; however, partial damage remained around the macula on SD-OCT, and an adaptive optics imaging system showed damaged cone photoreceptors. CONCLUSIONS: Prednisolone is an effective treatment for a disease that is believed to be due to suspicious involvement of the autoimmune system. Even severe outer retinitis can recover completely with rapid diagnosis and treatment.

RP2-associated retinal disorder in a Japanese cohort: Report of novel variants and a literature review, identifying a genotype-phenotype association.

The retinitis pigmentosa 2 (RP2) gene is one of the causative genes for X-linked inherited retinal disorder. We characterized the clinical/genetic features of four patients with RP2-associated retinal disorder (RP2-RD) from four Japanese families in a nationwide cohort. A systematic review of RP2-RD in the Japanese population was also performed. All four patients were clinically diagnosed with retinitis pigmentosa (RP). The mean age at examination was 36.5 (10-47) years, and the mean visual acuity in the right/left eye was 1.40 (0.52-2.0)/1.10 (0.52-1.7) in the logarithm of the minimum angle of resolution unit, respectively. Three patients showed extensive retinal atrophy with macular involvement, and one had central retinal atrophy. Four RP2 variants were identified, including two novel missense (p.Ser6Phe, p.Leu189Pro) and two previously reported truncating variants (p.Arg120Ter, p.Glu269CysfsTer3). The phenotypes of two patients with truncating variants were more severe than the phenotypes of two patients with missense variants. A systematic review revealed additional 11 variants, including three missense and eight deleterious (null) variants, and a statistically significant association between phenotype severity and genotype severity was revealed. The clinical and genetic spectrum of RP2-RD was illustrated in the Japanese population, identifying the characteristic features of a severe form of RP with early macular involvement.

Incidence of Axillary Nerve Injury After Arthroscopic Shoulder Stabilization.

PURPOSE: To investigate the incidence of axillary nerve palsy after arthroscopic shoulder stabilization and to measure the distance between the nerve and capsule in shoulders with a capsular lesion. METHODS: This retrospective study included 2,027 shoulders (1,909 patients; 1,433 male and 476 female patients; mean age, 32 years [age range, 13-81 years]) subjected to arthroscopic soft-tissue stabilization for recurrent shoulder instability from 2005 to 2017. The exclusion criteria were bone grafting or transfer and preoperative axillary nerve symptoms. We retrospectively reviewed patient records and investigated the incidence and clinical features of axillary nerve palsy. We measured the closest distance between the axillary nerve and capsule on preoperative magnetic resonance images. RESULTS: Postoperative axillary nerve palsy occurred in 4 shoulders (0.2% of all arthroscopic stabilizations). Capsular repair was performed in 2 shoulders (1.2% of 160 capsular repairs); humeral avulsion of the glenohumeral ligament (HAGL) repair, 1 shoulder (2% of 47 HAGL repairs); and isolated Bankart repair, 1 shoulder (0.05% of 1,941 Bankart repairs). The closest distance between the nerve and capsule was 3.4 ± 3.2 mm in shoulders with capsular or HAGL lesions and less than 1 mm in the 3 shoulders with palsy. The common symptoms in axillary nerve palsy cases were shoulder discomfort, delayed recovery of range of motion, and deltoid weakness and atrophy. A definitive diagnosis was made with electromyography in all cases. Nerve injury by a suture was confirmed during revision surgery in 3 shoulders subjected to capsular or HAGL repair during the initial operation. The palsy was transient and fully recovered in 1 shoulder with isolated Bankart repair. CONCLUSIONS: The incidence of axillary nerve palsy after arthroscopic soft-tissue shoulder stabilization was low but higher in shoulders subjected to capsular or HAGL repair. We should always consider the possibility of axillary nerve palsy in shoulders that require capsular or HAGL repair. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Ulnar neuropathy at the elbow in 413 Japanese patients: An assessment of pathological elbow lesions and neurological severity.

BACKGROUND: Various pathological elbow lesions are often complicated with ulnar neuropathy at the elbow (UNE), although the precise pathology, incidence, and clinical and neurological features of these lesions have not been identified. We therefore investigated elbow pathology and neurological severity in Japanese patients with UNE. METHODS: The medical records of 457 Japanese UNE patients who were surgically treated among 6 hospitals were retrospectively examined. Eligible patients had UNE diagnosed by physical findings and nerve conduction studies according to the criteria of the American Association of Electrodiagnostic Medicine. The elbows were analyzed with regard to age, gender, occupation, pathology at the elbow, and severity of nerve palsy. RESULTS: A total of 398 patients with 413 UNE elbows of a mean age of 63 years (range: 15-87) met the inclusion criteria. UNE elbows were predominantly in male patients (69.0%). Overall, 310 elbows (75.1%) had 1 or more elbow lesions: 238 elbows (76.8%) had a single lesion and 72 elbows (23.3%) had 2 or more lesions. The most common lesion was primary elbow osteoarthritis (EOA) occurring in 54.5% of elbows, followed next by medial elbow ganglion in 8.5% and cubitus valgus in 6.5%. Most elbows with medial elbow ganglion or cubitus valgus were associated with EOA. Entrapment sites were at the cubital tunnel in 84.5%-91.3% of UNE elbows, regardless of an association with elbow lesion. The incidence of McGowan grade III lesion was 50.8% in elbows with primary EOA, which was higher than the 35.0% in elbows with no lesion. CONCLUSIONS: This study revealed that UNE had various isolated or combined elbow lesions. In Japanese UNE, primary or secondary EOA was found in 62.2% of cases and severe motor weakness was noted in 47.2%. The incidences of EOA and severe ulnar nerve palsy in the Japanese UNE are higher than those in Caucasians. LEVEL OF EVIDENCE: Level IV; Prognostic-Investigating the effect of a patient characteristic on the outcome of a disease; Case series.

Clinical Course and Electron Microscopic Findings in Lymphocytes of Patients with DRAM2-Associated Retinopathy.

DRAM2-associated retinopathy is a rare inherited retinal dystrophy, and its outcome has not been determined. A single retinal involvement by a mutation of the DRAM2 gene is unexplained. We found three unrelated patients with a disease-causing DRAM2 variant in a biallelic state from 1555 Japanese individuals of 1314 families with inherited retinal dystrophy. We reviewed their medical records and examined their peripheral lymphocytes by transmission electron microscopy (TEM). Patient 1 was a 38-year-old woman who complained of night blindness and reduced vision. She developed macular degeneration at age 43 years. Patients 2 and 3 were a man and a woman both of whom noticed night blindness in their 30s. Both had a degeneration in the macula and midperiphery in their 40s, which progressed to a diffuse retinal degeneration in their 60s when their vision was reduced to hand motions. Three novel DRAM2 variants were identified. TEM of the lymphocytes of Patients 1 and 2 showed abnormal structures in 40.6% and 0.3% of the peripheral lymphocytes, respectively. We concluded that the DRAM2-associated retinopathy of our patients was a progressive rod-cone dystrophy, and the visual outcome was poor. The systemic effect of DRAM2 mutations may be compensable and have variations.

Variant course of extensor pollicis brevis tendon in the third extensor compartment.

INTRODUCTION: According to the anatomical literature, the extensor pollicis brevis (EPB) tendon passes through the first compartment and enters the base of the proximal phalanx of the thumb. There have been a few reports on the different types of supernumerary EPB tendons; however, an unusual course of the EPB tendon is extremely rare. MATERIALS AND METHODS: During routine cadaveric dissection in the Department of Gross Anatomy, we detected an variant EPB muscle in a 96-year-old fresh female cadaver. RESULTS: The EPB muscle originated from the posterior surface of the radius and interosseous membrane. However, the EPB tendon passed through the third compartment instead of the first compartment. It ran parallel to the extensor pollicis longus (EPL) tendon and entered the base of the thumb proximal phalanx. The EPL tendon was attached to the base of the first distal phalanx, as normally observed. Both EPB and EPL muscles were innervated by the posterior interosseous nerve. CONCLUSIONS: We report a case of a variant course of the EPB tendon appearing in the third extensor compartment of the wrist with the EPL tendon. The knowledge of this anatomic variation will be helpful for accurate diagnosis and surgical planning.

Ultrasonography could be used to predict extended insertion of the EPB tendon noninvasively.

INTRODUCTION: An abnormal distal insertion of the extensor pollicis brevis (EPB) tendon into the thumb interphalangeal joint (IP) has been observed in refractory cases of de Quervain's disease. This is associated with the extensor being wider at the midpoint of the proximal phalanx; however, there is no method to noninvasively measure this. This study evaluated the accuracy of measuring the extensor width using ultrasonography, to establish a noninvasive method for predicting an EPB extending the IP insertion. MATERIALS AND METHODS: Of 23 arms from 12 fresh frozen cadavers, the extensor tendon width at the midpoint of the proximal phalanx was measured using ultrasonography and directly at dissection. The association between these values was evaluated using correlation analysis. A cut-off value of extensor tendon width was obtained using receiver operating characteristic analysis. RESULTS: A strong correlation was observed between the ultrasonography and the measured values. The EPB tendons were normal in 13 arms (57%) and extended in 10 (43%), with a significant difference between these groups in the mean width of the extensor tendon (6.8 ± 1.1 vs. 8.4 ± 1.0 mm). A cut-off extensor tendon width of 8.0 mm yielded an EPB extending the IP. CONCLUSION: An EPB extending the IP tendon can be predicted by measuring the extensor tendon width at the midpoint of the proximal phalanx using ultrasonography. The cut-off tendon width value of ≥ 8.0 mm may be useful for assessments prior to surgery and for conservative care.

Identification of vitreous proteins in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a disorder of blood vessels in the retina developed in premature infants and the leading cause of the blindness in children. Proteomic analysis was performed to identify vitreous proteins specific to patients with ROP. Vitreous humor samples were obtained from three patients with ROP and two patients with congenital cataract, the latter included as a control group. The vitreous samples were separated by 2D-PAGE and the proteins running as definitive spots were identified by MALDI-TOF MS spectrometry. We identified 13 and 6 proteins in the vitreous from ROP and cataract patients, respectively. Albumin, transferrin, pigment epithelium-derived factor (PEDF) and transthyretin were found in both patient groups. In the samples from ROP patients, PEDF and transthyretin levels were lower than in those from cataract patients, and retinol binding protein 3 and prostaglandin D synthase were not detected. Of the 13 proteins, 9 proteins including α-2-macroglobulin, ceruloplasmin, α-fetoprotein, vitamin D-binding protein, α-1-antitrypsin, α-1-ß-glycoprotein, hemopexin, apolipoprotein A-1 and A-lV were found in vitreous samples of only the ROP patients. PEDF has anti-angiogenic and neurotrophic functions. Whether PEDF is increased or decreased in diabetic retinopathy has been controversial but we observed lower PEDF in the ROP samples than in the controls. The proteins specific to or decreased in ROP, if confirmed in future studies, may provide clue to understanding its pathogenesis.