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  1. Wern-Yih C, Fazilawati Q, Rahmat J, Shatriah I
    Korean J Ophthalmol, 2022 Jan 24.
    PMID: 35067016 DOI: 10.3341/kjo.2021.0116
    Purpose: The prevalence of retinopathy of prematurity (ROP) is higher in developing countries compared to developed countries. There is limited data on vision-related quality of life (VRQoL) among children with severe type of ROP in developing countries. This study evaluated the influence of threshold and pre-threshold ROP on VRQoL in Malaysian children.

    Methods: Multicenter prospective cross-sectional study conducted in three tertiary hospitals in 2018 to 2019. Children less than seven years old with previous ROP diagnosis were recruited and divided into threshold, high-risk and low-risk pre-threshold subgroups. Patients with systemic comorbidities that affected vision or daily activities were excluded. A parent/guardian completed the Children's Visual Function Questionnaire (CVFQ) for the assessment of child's general health, general vision, competence, personality, family impact and treatment difficulty.

    Results: Eight were categorized with threshold ROP, 16 with high-risk pre-threshold ROP, and 26 with low-risk pre-threshold ROP. 50 age-matched controls were also included. Mean visual acuity in logMAR was 0.46 in the threshold, 0.08 in high risk pre-threshold and 0.01 in low-risk pre-threshold subgroups. Threshold ROP was associated with myopia and strabismus, and associated with poor visual acuity compared to pre-threshold ROP. Mean total CVFQ score was significantly lower in the ROP group (p<0.001) compared to the control group. Mean score and all mean subscale scores were significantly lower in the threshold subgroup compared to high-risk and low-risk pre-threshold subgroups, with lowest subscale scores on general vision and general health. There was significant association between gestational age, visual acuity of the better eye and family income and VRQoL (p<0.05).

    Conclusion: ROP was associated with lower VRQoL in children born prematurely in Malaysia. The threshold ROP group is the most affected. General vision and health domains are their main difficulties encountered. Gestational age, visual acuity of the better eye and family income affects the VRQoL.

  2. Wai YZ, Radhakrishnan DM, Lingam G, Hamzah N, Rahmat J
    Taiwan J Ophthalmol, 2023;13(4):527-534.
    PMID: 38249495 DOI: 10.4103/tjo.TJO-D-22-00162
    PURPOSE: We aimed to analyze our 4-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) and to examine the tumor response, globe salvage, mortality, and safety profile of IAC in the Malaysian profile.

    MATERIALS AND METHODS: This was a retrospective, interventional case series. A total of 22 eyes of 20 patients with RB who underwent IAC using melphalan and topotecan from January 2018 to December 2021 in Hospital Kuala Lumpur were retrospectively reviewed. Tumor response, globe salvage, mortality, and safety profile of IAC were compared based on the International Classification of Retinoblastoma.

    RESULTS: The mean patient age at IAC was 21.3 months. An overall globe salvage rate of 63.6% was observed: more specifically, 100% for Group A, 75% for Groups B and C, 66.7% for Group D, and 42.9% for Group E. Poor tumor response after IAC was significantly associated with a lesser chance of globe salvage (P = 0.045). The overall rate of good tumor response following IAC was 77.3%. Specifically, rates of good tumor response in each group were 100%, 75%, 75%, 83.3% and 71.4% in group A, B, C, D and E, respectively. The mortality rate was 5%. Complications (per-catheterization) included cerebral infarct (2.2%), oxygen desaturation (2.2%), vomiting (26.1%), periorbital edema (8.8%), ptosis (6.5%), fever, femoral hematoma, and hyperpigmentation over lid (4.4% each).

    CONCLUSION: Four-year experience showed that IAC is a safe and effective method for RB management. Patients with a poor response after IAC may have a lower chance of globe salvage. Careful patient selection is of utmost importance to achieve the best outcome in a setting of limited health-care resources.

  3. Subramaniam S, Rahmat J, Rahman NA, Ramasamy S, Bhoo-Pathy N, Pin GP, et al.
    Asian Pac J Cancer Prev, 2014;15(18):7863-7.
    PMID: 25292078
    BACKGROUND: Retinoblastoma is a rare type of cancer that usually develops in early childhood. If left untreated it can cause blindness and even death. The aim of this study is to determine sociodemographic and clinical features of retinoblastoma patients and also to determine the treatment pattern and outcome in Malaysia.

    MATERIALS AND METHODS: Data for this study were retrieved from the Retinoblastoma Registry of the National Eye Database (NED) in Malaysia. Hospital Kuala Lumpur, Hospital Umum Kuching, Sarawak and Hospital Queen Elizabeth, Kota Kinabalu were the major source data providers for this study. Data collected in the registry cover demography, clinical presentation, modes of treatment, outcomes and complications.

    RESULTS: The study group consisted of 119 patients (162 eyes) diagnosed with retinoblastoma between 2004 and 2012. There were 68 male (57.1%) and 51 (42.9%) female. The median age at presentation was 22 months. A majority of patients were Malays (54.6%), followed by Chinese (18, 5%), Indians (8.4%), and indigenous races (15.9%). Seventy six (63.8%) patients had unilateral involvement whereas 43 patients had bilateral disease (36.1%). It was found that most children presented with leukocoria (110 patients), followed by strabismus (19), and protopsis (12). Among the 76 with unilateral involvement (76 eyes), enucleation was performed for a majority (79%). More than half of these patients had extraocular extension. Of the 40 who received chemotherapy, 95% were given drugs systemically. Furthermore, in 43 patients with bilateral involvement (86 eyes), 35 (41%) eyes were enucleated and 17 (49%) showed extraocular extension. Seventy-two percent of these patients received systemic chemotherapy. The patients were followed up 1 year after diagnosis, whereby 66 were found to be alive and 4 dead. Sixteen patients defaulted treatment and were lost to follow-up, whereas follow-up data were not available in 33 patients.

    CONCLUSIONS: Patients with retinoblastoma in this middle-income Asian setting are presenting at late stages. As a result, a high proportion of patients warrant aggressive management such as enucleation. We also showed that a high number of patients default follow-up. Therefore, reduction in refusal or delay to initial treatment, and follow-up should be emphasized in order to improve the survival rates of retinoblastoma in this part of the world.
  4. Chew FLM, Qurut SE, Hassan I, Lim ST, Ramasamy S, Rahmat J
    Med J Malaysia, 2019 02;74(1):15-19.
    PMID: 30846656
    INTRODUCTION: Paediatric cataract surgery is challenging with reported post-operative visual acuity (VA) of 0.3LogMar or better varying between 33% to 68% of patients.

    OBJECTIVE: The aim is to document the post-operative refraction, VA and complications of non-traumatic pediatric cataract surgery performed in a tertiary referral center in Malaysia.

    METHODOLOGY: This retrospective study reviewed case notes of all consecutive patients aged 12 years and below who underwent cataract surgery from January 2010 to December 2015. Patients were recruited if they had a minimum of six months post-operative follow-up. Exclusion criteria included traumatic cataract, central nervous system abnormalities, incomplete medical records or pre-existing ocular pathology. Subjects were divided into two groups based on refraction at one month. Subjects with refraction within 1- dioptre of the targeted spherical equivalent were in the success group and the rest were in the failure group.

    RESULTS: A total of 111 subjects were recruited (65 subjects in success group and 46 subjects in the failure group). Mean age at surgery was 33.14 (SD: 33.47) months. The success group had significantly longer axial length (p:0.0045, CI: 0.566-0.994, OR: 0.750). At final review, 44.1%(49/111) subjects had visual acuity of 0.3LogMar or better. The success group had better final mean VA in comparison to the failure group (p:0.034, CI:1.079-7.224, OR: 2.791).

    CONCLUSION: The outcome of non-traumatic paediatric cataract surgery was acceptable with 58.6% achieved targeted refractive correction at 1-month post-operative period. Longer axial length was associated with better refractive outcome. Capsule related complications was the most common intra-operative complication.

  5. Liu CC, Mohmood A, Hamzah N, Lau JH, Khaliddin N, Rahmat J
    PLoS One, 2020;15(5):e0232249.
    PMID: 32357178 DOI: 10.1371/journal.pone.0232249
    AIM: To report our first three-and-a-half years' experience with intra-arterial chemotherapy (IAC) in managing retinoblastoma (RB).

    METHODS: Single institution, retrospective, interventional case series of 14 retinoblastoma patients managed with IAC from December 2014 to June 2018. Demographics were described. Outcomes measures were tumor response, treatment complications and globe salvage.

    RESULTS: Subjects' mean age at the first administration of IAC was 31.4 months. 57.1% of the eyes were Group D and E retinoblastoma, while 79% were bilateral disease. 93% of the eyes were as secondary treatment. Of 32 IAC cannulations performed, 23 (71.8%) were successful and received chemotherapy drug melphalan. Each eye received a mean of 1.8 (range 1-4) IAC injections. 53% of the eyes showed regression post treatment. After a mean follow up period of 19 months, globe salvage rate was 38%. Most of the adverse effects experienced were localized and transient.

    CONCLUSION: IAC has provided an added recourse in the armamentarium of retinoblastoma treatment in our center. IAC treatment is a viable alternative in the treatment of retinoblastoma to salvage globe, for eyes that would conventionally require enucleation especially in bilateral disease.

  6. Cheah JASS, Tharmathurai S, Bahari NA, Rahmat J, Muhammed J
    Cureus, 2022 Oct;14(10):e30470.
    PMID: 36415378 DOI: 10.7759/cureus.30470
    Duane retraction syndrome (DRS) with mechanical and innervational upshoot poses a surgical challenge. We discuss a case of DRS with mechanical and innervational upshoot and its surgical management. An 11-year-old boy presented with left eye upward deviation since birth. This deviation was worst on the right gaze. His best corrected visual acuity was 6/6 OD and 6/60 OS. Refraction showed low hyperopia with low astigmatism in both eyes. Stereoacuity was absent and there was suppression on the Worth 4 dot test in the left eye. The left eye had large hypertropia of 50 prism diopter in primary gaze. Extraocular movements showed severe upshoot and narrowing of palpebral fissures on adduction and limited abduction (-2). The patient underwent Y-splitting of the left lateral rectus (LR) muscle of 10 mm, LR recession of 4 mm, and left eye superior rectus recession of 12 mm. A marked reduction in hypertropia in primary gaze was observed on day one and at two months postoperatively with residual upshoot on adduction. His left eye deviation remained stable after six months postoperatively.
  7. Chew FLM, Thavaratnam LK, Shukor INC, Ramasamy S, Rahmat J, Reidpath DD, et al.
    Med J Malaysia, 2018 02;73(1):25-30.
    PMID: 29531199 MyJurnal
    INTRODUCTION: Little is known regarding the extent of visual impairment amongst pre-school children in Malaysia.

    OBJECTIVE: To determine the prevalence of visual impairment and amblyopia in Malaysian preschool children.

    METHODOLOGY: A cross-sectional, population-based study was conducted on children aged four to six years from 51 participating kindergartens in the district of Segamat, Johor, Malaysia from 20 March 2016 to 6 April 2016. All subjects had initial eye screening consisting of LogMar visual acuity, orthoptics examination and Spot vision screener assessment. Subjects who failed the initial eye screening were invited for a formal eye assessment consisting of cycloplegic refraction and a comprehensive ocular examination. Definitions of visual impairment and amblyopia were based on the Multi-Ethnic Pediatric Eye Disease Study criteria.

    RESULTS: A total of 1287 children were recruited. Mean subject age was 5.03 (SD:0.77) and males represented 52.3% of subjects. Subjects by ethnicity were Malay (54.8%), Chinese (27.7%), Indian (15.6%) and Orang Asli (1.9%). Formal eye assessment was required for 221 subjects and 88.8% required ophthalmic intervention. Refractive error, representing 95.4% of diagnosed ocular disorders, comprised of astigmatism (84%), myopia (9%) and hypermetropia (6.9%). With-the-rule astigmatism was present in 93.4% of the subjects with astigmatism. Visual impairment was present in 12.5% of our subjects, with 61% having bilateral visual impairment. Of the subjects with visual impairment, 59.1% had moderate visual impairment. The prevalence of amblyopia was 7.53%, and 66% of the amblyopic subjects had bilateral amblyopia.

    CONCLUSION: Our study highlights an urgent need for initiation of preschool vision screening in Malaysia.

  8. Poh KW, Wai YZ, Rahmat J, Shunmugam M, Alagaratnam J, Ramasamy S
    Int J Ophthalmol, 2017;10(3):488-490.
    PMID: 28393045 DOI: 10.18240/ijo.2017.03.26
  9. Teow Kheng Leong K, Abu Kassim SNA, Sidhu JK, Zohari Z, Sivalingam T, Ramasamy S, et al.
    BMC Ophthalmol, 2021 Mar 09;21(1):128.
    PMID: 33750348 DOI: 10.1186/s12886-021-01882-x
    BACKGROUND: The current practice for new-born eye examination by an Ophthalmologist in Malaysian hospitals is limited to only preterm new-borns, syndromic or ill infants. Healthy term new-borns are usually discharged without a thorough eye examination. This study is aimed at determining the proportion and types of ocular abnormalities detected in purportedly healthy term new-borns.

    METHOD: This cross-sectional study is comprised of 203 participants, all purportedly healthy term new-born infants from the Obstetrics and Gynaecology ward at Hospital Kuala Lumpur over a 6 months period. The examination list includes external eye examination, red reflex test, and fundus imaging using a wide-field digital retinal imaging system (Phoenix Clinical ICON Paediatric Retinal Camera) by a trained Investigator. The pathologies detected were documented. The results were compared and correlated with similar studies published in the literature previously.

    RESULTS: Total ocular abnormalities were detected in 34% of the infants. The most common finding was retinal haemorrhage in 29.6% of the infants, of which 53.3% occurred bilaterally. Spontaneous vaginal delivery (SVD) remained the greatest risk factor which has nearly 3.5 times higher risk of new-borns developing retinal haemorrhage compared to Lower Segment Caesarean Section (LSCS). There was a 6% increased likelihood of developing retinal haemorrhage for every 1-min increment in the duration of 2nd stage of labour.

    CONCLUSION: Universal eye screening for all new-borns using a wide-field digital imaging system is realistically possible, safe, and useful in detecting posterior segment disorders. The most common abnormality detected is retinal haemorrhage.

  10. Mohd Khalid MK, Yakob Y, Md Yasin R, Wee Teik K, Siew CG, Rahmat J, et al.
    Mol Vis, 2015;21:1185-90.
    PMID: 26539030
    The availability of molecular genetic testing for retinoblastoma (RB) in Malaysia has enabled patients with a heritable predisposition to the disease to be identified, which thus improves the clinical management of these patients and their families. In this paper, we presented our strategy for performing molecular genetic testing of the RB1 gene and the findings from our first 2 years of starting this service.
  11. Wardati H J, Khadijah M, Nurul-Farhana M, Karimmah W, Lai YKI, Syahmi MR, et al.
    Cureus, 2024 Jul;16(7):e63712.
    PMID: 38966779 DOI: 10.7759/cureus.63712
    PURPOSE: This study aimed to evaluate the treatment efficacy, anatomical outcomes, and refractive outcomes of laser photocoagulation (LPC) and intravitreal ranibizumab (IVR) in the treatment of type I retinopathy of prematurity (ROP) at one-year follow-up.

    METHODS: This is a retrospective study on the treatment of type I ROP and aggressive ROP (A-ROP) using LPC or IVR in three Malaysian hospitals providing pediatric ophthalmology services from January 2019 to December 2021. Information on gestational age, birth weight, ROP zone and stage, and underlying comorbidities was collected. Parameters for evaluating treatment efficacy include the time taken to achieve complete regression, the regression rate, and the reactivation rate. The anatomical and refractive outcomes were evaluated at one year of adjusted age.

    RESULTS: This study included 92 eyes from 46 infants. Of these, 42 eyes received LPC as the initial treatment, while 50 eyes underwent IVR. A higher percentage of infants with cardiovascular disease were treated with IVR (66.7%) compared to LPC (40%) (p<0.05). However, there were no significant differences in gestational age, birth weight, respiratory distress syndrome, sepsis, or intraventricular hemorrhage between the two treatment groups (p>0.05). Infants treated with LPC had a higher regression rate than those treated with IVR, but they were also significantly more myopic and had worse best-corrected visual acuity (BCVA). Conversely, infants treated with IVR experienced a significantly higher reactivation rate compared to those treated with LPC. Logistic regression analysis showed no significant associations between gestational age, birth weight, plus disease, zone 1 ROP, and the choice of initial treatment with the reactivation of ROP.

    CONCLUSIONS: Both LPC and IVR effectively treat type I ROP in infants, with IVR yielding superior anatomical and refractive outcomes and LPC offering a lower reactivation rate. Understanding individual patient characteristics is crucial for treatment selection.

  12. Hall HN, Bengani H, Hufnagel RB, Damante G, Ansari M, Marsh JA, et al.
    PLoS One, 2022;17(11):e0268149.
    PMID: 36413568 DOI: 10.1371/journal.pone.0268149
    Classical aniridia is a congenital and progressive panocular disorder almost exclusively caused by heterozygous loss-of-function variants at the PAX6 locus. We report nine individuals from five families with severe aniridia and/or microphthalmia (with no detectable PAX6 mutation) with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. These mutations occurred de novo in 3/5 families, with the remaining families being compatible with autosomal dominant inheritance. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes. Substitutions of the same codon (Arg51) in MAB21L2, a close homolog of MAB21L1, cause severe ocular and skeletal malformations in humans and mice. The predicted nucleotidyltransferase function of MAB21L1 could not be demonstrated using purified protein with a variety of nucleotide substrates and oligonucleotide activators. Induced expression of GFP-tagged wildtype and mutant MAB21L1 in human cells caused only modest transcriptional changes. Mass spectrometry of immunoprecipitated protein revealed that both mutant and wildtype MAB21L1 associate with transcription factors that are known regulators of PAX6 (MEIS1, MEIS2 and PBX1) and with poly(A) RNA binding proteins. Arg51 substitutions reduce the association of wild-type MAB21L1 with TBL1XR1, a component of the NCoR complex. We found limited evidence for mutation-specific interactions with MSI2/Musashi-2, an RNA-binding proteins with effects on many different developmental pathways. Given that biallelic loss-of-function variants in MAB21L1 result in a milder eye phenotype we suggest that Arg51-altering monoallelic variants most plausibly perturb eye development via a gain-of-function mechanism.
  13. Global Retinoblastoma Study Group, Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, et al.
    JAMA Oncol, 2020 May 01;6(5):685-695.
    PMID: 32105305 DOI: 10.1001/jamaoncol.2019.6716
    IMPORTANCE: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

    OBJECTIVES: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.

    DESIGN, SETTING, AND PARTICIPANTS: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.

    MAIN OUTCOMES AND MEASURES: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.

    RESULTS: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).

    CONCLUSIONS AND RELEVANCE: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

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