Susmito Biswas

X-linked retinoschisis: an update

X-linked retinoschisis is the leading cause of macular degeneration in males and leads to splitting within the inner retinal layers leading to visual deterioration. Many missense and protein truncating mutations have now been identified in the causative retinoschisis gene (RS1) which encodes a 224 amino acid secreting retinal protein, retinoschisin. Retinoschisin octamerises is implicated in cell–cell interactions and cell adhesion perhaps by interacting with β2 laminin. Mutations cause loss of retinoschisin function by one of the three mechanisms: by interfering with protein secretion, by preventing its octamerisation or by reducing function in the secreted octamerised protein. The development of retinoschisis mouse models have provided a model system that closely resembles the human disease. Recent reports of RS1 gene transfer to these models and the sustained restoration of some retinal function and morphology suggest gene replacement may be a possible future therapy for patients.

The ocular features of the mucopolysaccharidoses

AimsThe mucopolysaccharidoses (MPS) are a heterogeneous group of rare disorders characterised by accumulation of glycosaminoglycans within multiple organ systems. This study aimed to determine the prevalence and severity of ocular complications in patients with MPS.MethodsClinical ophthalmic features and electrodiagnostic results of 50 patients with a diagnosis of MPS were retrospectively reviewed.ResultsA total of 79% of MPS IH patients had a visual acuity of less than 6/12 equivalent in their better eye, compared to 44% of MPS IH/S and 25% of MPS VI patients. In total, 16% of MPS IH and 25% of MPS IH/S had severe corneal opacification, compared to 38% of MPS VI patients. 16% of MPS IH patients had optic atrophy; 21% of MPS VI patients had mild disc swelling, 29% had markedly swollen discs, and 14% had optic atrophy. One patient with MPS IH, one with MPS IH/S and six with MPS VI had ocular hypertension. One MPS VI patient had glaucoma that required topical therapy. Nine patients with MPS IH had electrodiagnostic evidence of retinopathy, as did one MPS VI patient.ConclusionsOcular complications causing significant reduction in vision are common in MPS. The majority of MPS I and MPS VI patients have corneal opacification, which can lead to difficulties in diagnosis and monitoring of glaucoma, optic disc changes, and retinopathy.

Advances in the management of congenital and infantile cataract

Congenital and infantile cataracts produce deprivation amblyopia and can thus cause lifelong visual impairment. Successful management is dependent on early diagnosis and referral for surgery when indicated. Accurate optical rehabilitation and postoperative supervision are essential.The timing of surgery and its relationship to the duration of deprivation is important. Unilateral congenital cataract surgery within 6 weeks of birth produces the best outcomes. The equivalent ‘latent’ period for bilateral visual deprivation may be longer at around 10 weeks.Visual deprivation has a significant impact on the development of fixation stability. Major form deprivation, even after early surgery, leads to nystagmus. This is mostly manifest latent nystagmus (MLN). The latent period for fixation stability may be as short as 3 weeks. Preoperative congenital nystagmus (CN) can convert to more benign MLN after surgery.Infantile IOL implantation is becoming increasingly accepted. A satisfactory long-term refractive result requires that allowance be made for childhood axial growth and myopic shift. In a series of 25 infants (33 eyes) implanted before 12 months of age, the mean myopic shift at 12 months was 4.83 D. This increased to 5.3 D in infants implanted before 10 weeks. The initial desired refractive outcome following IOL implantation is thus hypermetropia, with the degree dependent on the age of the child.Glaucoma or ocular hypertension is a common complication following paediatric cataract surgery. Microphthalmia and surgery in early infancy are risk factors. Tonometry results may be influenced by the increased corneal thickness seen in aphakic and pseudophakic children. The long-term prognosis of eyes with aphakic glaucoma is not necessarily poor but intraocular pressure control may require three or more medications. Surgical intervention appears to be necessary in over a quarter of eyes.Posterior capsule opacification (PCO) is common in infants undergoing primary lens implantation. Primary capsulotomy and anterior vitrectomy reduce the risk of PCO. In the absence of anterior vitrectomy, primary posterior capsulotomy does not prevent visual axis opacification.Further developments will continue to be driven by clinical research. The prevention of capsule opacification and cellular proliferation may in future be achieved by the use of devices to specifically target epithelial cells at surgery.

Accuracy of intraocular lens power calculation in paediatric cataract surgery

AIMS To determine the accuracy of intraocular lens (IOL) power calculation in a group of pseudophakic children. METHODS A retrospective analysis of biometric and refractive data was performed on 52 eyes of 40 infants and children, who successfully underwent cataract extraction and IOL implantation. The following parameters were included: age at the time of surgery, keratometry, axial length, estimated refraction, and the power of IOL implanted. The postoperative refractive outcome was taken as the spherical equivalent of the refraction at 3 months after surgery. The prediction error was taken as the absolute difference between the estimated and actual postoperative refraction. The data were analysed to assess the effects of age at the time of surgery, keratometry, and axial length on the accuracy of calculation of IOL power. RESULTS For the overall group the mean and median prediction errors were 1.40 D and 0.84 D (SD 1.60). The mean and median prediction errors in eyes with axial lengths ⩾20 mm were 1.07 D and 0.71 D (SD 0.98) and in eyes <20 mm were 2.63 D and 2.61 D (SD 2.65). The mean and median prediction errors in eyes in children aged ⩾36 months were 1.06 D and 0.68 D (SD 1.02) and in children aged <36 months was 2.56 D and 2.29 D (SD 2.50). The differences between the prediction errors for both axial length and age were statistically significant (p<0.05). CONCLUSIONS For the overall group IOL power calculation is satisfactory. In eyes with axial lengths less than 20 mm and in children less than 36 months of age larger errors can arise. This study demonstrates the need for an IOL formula specifically designed for paediatric use.

Personalized diagnosis and management of congenital cataract by next-generation sequencing.

PURPOSE To assess the utility of integrating genomic data from next-generation sequencing and phenotypic data to enhance the diagnosis of bilateral congenital cataract (CC). DESIGN Evaluation of diagnostic technology. PARTICIPANTS Thirty-six individuals diagnosed with nonsyndromic or syndromic bilateral congenital cataract were selected for investigation through a single ophthalmic genetics clinic. METHODS Participants underwent a detailed ophthalmic examination, accompanied by dysmorphology assessment where appropriate. Lenticular, ocular, and systemic phenotypes were recorded. Mutations were detected using a custom-designed target enrichment that permitted parallel analysis of 115 genes associated with CC by high-throughput, next-generation DNA sequencing (NGS). Thirty-six patients and a known positive control were tested. Suspected pathogenic variants were confirmed by bidirectional Sanger sequencing in relevant probands and other affected family members. MAIN OUTCOME MEASURES Molecular genetic results and details of clinical phenotypes were identified. RESULTS Next-generation DNA sequencing technologies are able to determine the precise genetic cause of CC in 75% of individuals, and 85% patients with nonsyndromic CC were found to have likely pathogenic mutations, all of which occurred in highly conserved domains known to be vital for normal protein function. The pick-up rate in patients with syndromic CC also was high, with 63% having potential disease-causing mutations. CONCLUSIONS This analysis demonstrates the clinical utility of this test, providing examples where it altered clinical management, directed care pathways, and enabled more accurate genetic counseling. This comprehensive screen will extend access to genetic testing and lead to improved diagnostic and management outcomes through a stratified medicine approach. Establishing more robust genotype-phenotype correlations will advance knowledge of cataract-forming mechanisms.

Primary IOL implantation in children: a risk analysis of foldable acrylic v PMMA lenses

Background/aims: To compare the relative risks of poly (methylmethacrylate) (PMMA) and soft acrylic (AcrySof) primary intraocular lens (IOL) implantation in paediatric cataract surgery. Methods: A retrospective analysis of clinical data was performed on eyes of 61 infants and children who underwent cataract surgery with primary IOL implantation. Age at operation ranged from 3 weeks to 15 years. Mean follow up duration was 24.5 months (range 0.5–68 months). Factors examined included type of IOL (PMMA, acrylic), performance of a primary posterior continuous curvilinear capsulorhexis (PCCC) or capsulotomy with limited anterior vitrectomy, perioperative complications, and subsequent intervention for posterior capsule opacification (PCO). Risk factors for perioperative complications were examined with 2×2 tables to give odds ratios (OR) as measures of association. A survival analysis was performed to assess risk of subsequent intervention for PCO with different IOL types. Relative risks (hazards) and confidence intervals (CI) were calculated with Cox regression to adjust for potential confounding. Results: Compared to acrylic, PMMA IOLs were significantly associated with perioperative complications (OR 5.2, 95% CI 1.4 to 19, p = 0.01). However, IOL and type of section were highly correlated factors, and this finding may reflect risks associated with larger scleral wounds used for PMMA IOLs. No statistically significant difference in risk of subsequent intervention for PCO was found between different IOL types. Mean times till intervention for PMMA and acrylic IOLs were 30.1 months (95% CI 22 to 38) and 19.8 months (95% CI 12 to 27) respectively (log rank test statistic 1.53, one degree of freedom, p = 0.22). At 12 months post-implant surgery, 76% (95% CI 59 to 93) of PMMA cases and 54% (95% CI 35 to 72) of acrylic cases had not required intervention for PCO; these proportions fell to 55% (95% CI 35 to 75) and 38% (95% CI 14 to 61) for PMMA and acrylic cases respectively at 2 years post-surgery. After adjustment for age at surgery, primary posterior capsulorhexis, and perioperative complications relative risk of intervention after acrylic IOL implantation was 1.6 (95% CI 0.66 to 3.9, p = 0.29). Conclusion: Primary implantation of foldable soft acrylic IOLs in paediatric eyes may allow fewer perioperative complications than rigid PMMA IOLs. Short term safety profiles of primary implantation in paediatric cataract surgery are otherwise comparable for PMMA and soft acrylic IOLs.

Management of pellucid marginal corneal degeneration

Purpose A retrospective study to ascertain the management of pellucid marginal corneal degeneration (PMCD).Method and results Sixteen patients (average age 42.6 years) presented with PMCD. PMCD was bilateral in 13 and unilateral in 3 patients. Eight eyes underwent surgery. Nineteen eyes were managed non-surgically. Surgery involved corneal wedge excision (WE) (6 eyes), penetrating keratoplasty (PK) (3 eyes) and lamellar thermo-keratoplasty (LTK) (1 eye). Immediate pre-operative average visual acuity (VA) was 6/24, 6/10 and 6/60 with an average pre-operative astigmatism of 11.40 D, 9.75 D and 20.5 D for WE, PK and LTK respectively. After an average post-operative follow-up of 57 months, 66 months and 1 year, the average astigmatism was 8.90 D, 4.63 D and 6.00 D with an average final VA of 6/19, 6/15 and 6/6 for WE, PK and LTK respectively. In the nonsurgical group, at presentation, 40% of eyes had a VA of 6/12 or better. After an average follow-up period of 32.3 months, 80% of eyes had a visual acuity of 6/12 or better. Optical correction was achieved with spectacles and or contact lenses.Conclusions Surgical correction for PMCD provides poor long-term reduction of astigmatism. Patients with PMCD may be adequately corrected in the long term by the use of scleral fitted gas-permeable contact lenses.

Refractive outcomes after primary intraocular lens implantation in infants

Background: Intraocular lens (IOL) implantation is becoming increasingly accepted as a primary procedure in infants. Aim: To evaluate the accuracy of IOL power calculation, the rate of myopic shift and the refractive outcome after primary IOL implantation in infants aged <12 months at the time of cataract surgery. Method: A retrospective case review of 25 patients (8 with bilateral cataracts and 17 with unilateral cataracts) who underwent cataract surgery with primary IOL implantation at <12 months of age. Outcomes measured were actual early postoperative refraction, lens power calculation error, myopic shift and refractive outcome. Results: In 83% of cases, actual postoperative refraction was within 2 dioptres (D) of the target refraction. Lens power calculation error did not depend on axial length, age at surgery or target refraction. Mean (SD) myopic shift was 5.43 (3.7) D in the first 12 months after surgery, but was significantly greater when surgery was performed at <10 weeks of age. Conclusion: This study demonstrates that IOL power can be calculated with reasonable accuracy in infants using current formulas. Factors such as age at the time of surgery, axial length, whether surgery is unilateral or bilateral, and the presence of systemic pathologies do not seem to influence the accuracy of lens power calculation or myopic shift up to 36 months of age.

Scleral contact lens management of bilateral exposure and neurotrophic keratopathy.

We report an interesting case of therapeutic scleral lens management of bilateral exposure and neurotrophic keratopathy resulting from bilateral cranial nerve (CN) palsies including V, VI and VII, which caused lagophthalmos and anaesthetic corneas. Subsequent development of severe exposure keratitis with vascularisation and keratinisation of the inferior cornea was previously treated with intensive ocular lubrication, botulinum toxin injections to the upper eyelid levator muscle, temporary tarsorrhophies, bilateral amniotic membrane grafts, punctal plugs, lid taping, gold eyelid weights and soft bandage contact lenses. Corneal integrity was re-established but visual acuity remained significantly compromised by corneal vascularisation, scarring and keratin deposits. Visions on presentation to the contact lens department were R 1.90 logMAR, L 1.86 logMAR. Therapeutic, high Dk, non-fenestrated, saline filled, scleral lenses were fitted. Daily wear of these lenses have protected and hydrated the cornea, enabling corneal surface recovery whilst retaining visual and social function. The visual acuities 6 months post-scleral fitting with lenses in situ are R 0.90 logMAR and L logMAR 0.70.

The ophthalmic findings in Cohen syndrome

Aim: Cohen syndrome is an uncommon autosomal recessive condition comprising a characteristic facial appearance, mental retardation, benign neutropenia, and retinal dystrophy. This study aimed to identify patients with Cohen syndrome from across the United Kingdom in order to define the variability of ophthalmic manifestations. Methods: Ophthalmic assessment was undertaken and past ophthalmic records reviewed in 22 patients with classic features of Cohen syndrome. Results: All patients had visual problems which commonly started in the preschool years. 82% developed strabismus or refractive error during the first 5 years of life. 70% developed high myopia by the second decade. By contrast with the findings of others, early onset retinal dystrophy was common, occurring in 80% of study patients under age 5 years. 35% of patients were registered partially sighted or blind. Conclusion: The ophthalmic abnormalities associated with Cohen syndrome, including high myopia and a generalised, severe retinal dystrophy, are of early onset and frequently result in severe visual handicap. Cohen syndrome should be considered in the young, developmentally delayed child who presents with severe myopia and nyctalopia.