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  1. Lin H, Khaliddin N
    Cureus, 2023 Nov;15(11):e48129.
    PMID: 38046722 DOI: 10.7759/cureus.48129
    Acanthamoeba keratitis is a potentially sight-threatening infection of the cornea that can lead to blindness. Over the past few decades, there has been a rise in the reported cases worldwide, which is in line with the increase of contact lens wearers. Here, we present three cases of Acanthamoeba keratitis with different outcomes.
  2. Kamalden TA, Choo MM, Kadir K, Khaliddin N
    Neuroradiol J, 2009 Jan 20;21(6):861-4.
    PMID: 24257059
    Orbital arteriovenous malformation is a rare condition which poses a management problem in view of the complexity of the vessels involved, and the potentially blinding and life-threatening complications from the modes of treatment. Treatment requires obliteration of the abnormal vascular communication. Vision may be adversely affected by the condition itself, as well as a result of invasive treatment modalities. This case reports such a situation where the visual outcome was severely affected following embolization of the feeding vessels.
  3. Jamaluddin Ahmad M, Lott PW, Khaliddin N, Singh S
    Med J Malaysia, 2020 07;75(4):461-463.
    PMID: 32724020
    A 33-year-old man presented with a four-day history of redness and blurring of vision of the right eye. A clinical diagnosis of adenoviral keratitis was made with a differential of microsporidia epithelial keratitis. The patient subsequently developed nummular keratitis which was resistant to topical steroids. He continued to develop multiple recurrences of the condition. Treatment with tacrolimus ointment was started as the patient had an elevated intraocular pressure due to prolonged steroid use. Tacrolimus ointment showed a favourable outcome in the management of recurrent nummular keratitis.
  4. Ee CL, Mohd Abdullah AA, Samsudin A, Khaliddin N
    Ulus Travma Acil Cerrahi Derg, 2019 09;25(5):527-530.
    PMID: 31475330 DOI: 10.5505/tjtes.2018.57059
    Non-accidental injury (NAI) is not an uncommon problem worldwide, which leads to significant morbidity and mortality in infants. The presence of retinal or subdural haemorrhages, or encephalopathy with injuries inconsistent with the clinical history is highly suggestive of NAI. In this study, we report on a case of a a 3-month-old infant who presented to the casualty department with a very sudden onset of recurrent generalised tonic-clonic seizures. There was no history of trauma or visible external signs. She was found to have bilateral subdural haemorrhages and atypical unilateral ischaemic retinopathy. Retinal photocoagulation was performed with subsequent resolution of vitreous and retinal haemorrhages. However, visual recovery in that eye remained poor. The findings showed that a high index of suspicion of NAI is required in infants with intracranial haemorrhage and unilateral retinal haemorrhages.
  5. Low A, Chow RC, Ee Ling A, Khaliddin N
    Cureus, 2023 Jul;15(7):e41341.
    PMID: 37546106 DOI: 10.7759/cureus.41341
    A 72-year-old Chinese male presented with unilateral left eye panuveitis, then diagnosed as bilateral T-cell primary vitreoretinal lymphoma (T-PVRL) through chorioretinal biopsy and immunohistochemistry. No CNS nor systemic involvement was found at diagnosis. Despite initiating intravenous and intrathecal chemotherapy and intravitreal methotrexate, the disease eventually spread to the fellow eye with subsequent recurrence and systemic metastasis. To our knowledge, no cases of T-PVRL treated in a silicone-filled eye were reported in the literature. T- PVRL is exceedingly rare, with most PVRL being the malignant B-cell variant. This case highlights the challenges encountered throughout the treatment course of this aggressive entity, including the administration of intravitreal methotrexate in a silicone oil-filled eye. The poor overall survival rate and grim prognosis of T-PVRL are highlighted. Therefore, we recommend prompt tissue biopsy and immediate initiation of systemic chemotherapy and intravitreal methotrexate.
  6. Kai LC, Khaliddin N, Hassan MK, Hariri F
    Int Ophthalmol, 2024 Mar 19;44(1):147.
    PMID: 38499845 DOI: 10.1007/s10792-024-03084-y
    BACKGROUND: This study aims to compare the changes in ophthalmic parameters among syndromic craniosynostosis patients who underwent craniofacial skeletal expansion procedures via distraction osteogenesis (DO).

    METHOD: A retrospective study was conducted involving syndromic craniosynostosis patients who underwent surgical expansion via the DO technique from the year 2012 to March 2022. Changes in six parameters which consist of visual acuity, refractive error, optic disc health, intraocular pressure, degree of proptosis and orbital volume were measured objectively pre and post-surgery. For categorical parameters, the Chi-square cross-tab test was done. Paired sample T-test was used for normally distributed variables. Wilcoxon signed-rank test was used for non-normally distributed data.

    RESULTS: Visual impairment was present in 21.4% of eyes before surgery and increased to 28.5% post-surgery. Three patients had changes of refractive error post-surgery with one developed hypermetropia, another developed anisometropia and the last had improvement to no refractive error. Two patients had optic disc swelling which was resolved post-surgery. Intraocular pressure changes were inconsistent post-surgery. All patients achieved a significant reduction in the degree of proptosis post-surgery. Orbital volume calculation using computed tomography (CT) scans shows a significant increase in volume post-surgery for all patients.

    CONCLUSION: Our study shows a significant increase in orbital volume post-surgery with a reduction in the degree of proptosis. Optic disc and nerve health improved after the surgery. Changes in terms of visual acuity, refractive error and IOP were inconsistent after the surgical intervention.

  7. Amir NN, Kamaruzzaman SB, Effendi-Tenang I, Jamaluddin M, Tan MP, Ramli N, et al.
    Eur Geriatr Med, 2021 Apr;12(2):313-319.
    PMID: 33486745 DOI: 10.1007/s41999-021-00450-2
    PURPOSE: Using data from the Malaysian Elders Longitudinal Research (MELoR), this study investigated the association between visual function (visual acuity and contrast sensitivity) and frailty in a group of urban-dwelling older adults.

    METHODS: This was a cross-sectional study. 1332 participants aged ≥ 55 years were selected by random sampling from the parliamentary electoral register. Only 1274 participants completed the frailty assessment and 1278 participants completed the contrast sensitivity assessment. Impaired vision was defined as a Snellen visual acuity of worse than 6/12 in the better eye. Poor contrast sensitivity was defined as a score on the Pelli Robson chart of lower than 1.65. Frailty was defined with the Fried's phenotype criteria. Inter-group comparisons were determined with the independent T-test for continuous variables and the Pearson's Chi-squared test for categorical variables. The odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the cross-sectional association between frailty and visual function.

    RESULTS: The mean age of participants was 68.8 ± 7.5 years, of which 58.1% (774) were women. Impaired vision and poor contrast sensitivity were present in 187 (14%) and 271 (21.2%) subjects respectively. 73 (5.8%) individuals were classified as frail, 1161 (91.0.%) pre-frail, and 40 (2.8%) non-frail. There was no significant difference in frailty phenotypes between those with good and impaired vision (p = 0.241). Fried's component of handgrip strength, gait speed and exhaustion were significantly better in those with good visual function (p 

  8. Effendi-Tenang I, Tan MP, Khaliddin N, Jamaluddin Ahmad M, Amir NN, Kamaruzzaman SB, et al.
    Arch Gerontol Geriatr, 2020 06 26;90:104165.
    PMID: 32650156 DOI: 10.1016/j.archger.2020.104165
    INTRODUCTION: Published literature on vision impairment and cognitive function amongst older Malaysians remains scarce. This study investigates the association between vision impairment and cognitive function in an older Malaysian population.

    METHODS: Subjects aged 55 years and above from the Malaysian Elders Longitudinal Research (MELoR) study with available information on vision and Montreal Cognitive Assessment (MoCA) scores were included. Data were obtained through a home-based interview and hospital-based health check by trained researchers. Visual acuity (VA) was assessed with logMAR score with vision impairment defined as VA 6/18 or worse in the better-seeing eye. Cognition was evaluated using the MoCA-Blind scoring procedure. Those with a MoCA-Blind score of <19/22 were considered to have cognitive impairment.

    RESULTS: Data was available for 1144 participants, mean (SD) age = 68.57 (±7.23) years. Vision impairment was present in 143 (12.5 %) and 758 (66.3 %) had MoCA-Blind score of <19. Subjects with vision impairment were less likely to have a MoCA-Blind score of ≥19 (16.8 % vs 36.2 %, p < 0.001). Vision impairment was associated with poorer MoCA-Blind scores after adjustments for age, gender, and ethnicity (β = 2.064; 95 % CI, -1.282 to 3.320; P = 0.003). In those who had > 6 years of education attainment, vision impairment was associated with a significant reduction of cognitive function and remained so after adjustment for age and gender (β = 1.863; 95 % CI, 1.081-3.209; P = 0.025).

    CONCLUSION: Our results suggest that vision impairment correlates with cognitive decline. Therefore, maintaining good vision is an important interventional strategy for preventing cognitive decline in older adults.

  9. Jamaluddin Ahmad M, Maw Pin T, Khaliddin N, Effendi-Tenang I, Amir NN, Kamaruzzaman SB, et al.
    Asia Pac J Public Health, 2020 12 29;33(2-3):280-286.
    PMID: 33375833 DOI: 10.1177/1010539520983667
    Low vision and blindness are major health issues affecting ageing population. This cross-sectional study aims to determine the prevalence of visual impairment (VI) in Petaling Jaya North, Petaling Jaya South, and Lembah Pantai using data from the Malaysian Elders Longitudinal Research. There were 1322 participants aged ≥55 years selected by random sampling from parliamentary electoral rolls. Visual acuity was assessed using the logarithm of the minimum angle of resolution chart at 4 m distance. The overall population-adjusted prevalence of VI was 9.0%. The estimated prevalence of VI was highest in Malays followed by Indians and Chinese. Following adjustments for ethnic discrepancies in age, marital status, education level, gender and medical illness, the Malay ethnicity remained an independent association for VI. Education level was associated with Indian ethnicity. In conclusion, the Malay ethnicity and lower education level among Indian ethnicity were found to be associated with VI among the older population in Malaysia. The Malay ethnicity showed the highest prevalence of VI followed by Indians and Chinese.
  10. 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.

  11. Santiagu F, Bakhtiari A, Iqbal T, Khaliddin N, Lansingh VC, Subrayan V
    Int Ophthalmol, 2018 Oct;38(5):2069-2076.
    PMID: 28879527 DOI: 10.1007/s10792-017-0701-5
    BACKGROUND: Purpose of this study is to evaluate changes in the central corneal thickness (CCT) in patients during the third trimester and postpartum phases of normal pregnancy, pregestational diabetes mellitus (DM), and gestational diabetes mellitus (GDM).
    METHODS: This was a prospective study. Patients that fulfilled the inclusion criteria were recruited from the obstetric clinic. They were grouped into normal pregnancy, pregestational DM, and GDM. Ophthalmic assessment and haematological investigations were done during the third trimester (after 28 weeks of gestation) and in the postpartum phase (6 weeks postpartum).
    RESULTS: A total of 192 pregnant patients were recruited for this study. Out of the 192 patients, only 143 of them came back for their follow-up 6 weeks postpartum. A total of 70 (36.5%) normal pregnancy patients, 51 (26.6%) DM patients, and 71 (36.9%) GDM patients were included in this prospective study. Our study showed that the CCT decreased postpartum in all three groups. Patients in all three groups did not have significantly different CCT during the third trimester of pregnancy and postpartum phase. However, patients who had thicker CCT irrespective of the grouping during the third trimester also had a thicker CCT post-delivery (p value <0.001). However, these changes did not appear to affect refractive error and visual acuity.
    CONCLUSIONS: Diabetes mellitus during pregnancy did not appear to influence the CCT.
    Study site: Obstetrics clinic, University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia
  12. Choo MM, Yeong CM, Grigg JR, Khaliddin N, Kadir AJ, Barnes EH, et al.
    Medicine (Baltimore), 2018 Nov;97(48):e13357.
    PMID: 30508927 DOI: 10.1097/MD.0000000000013357
    To report observations of horizontal corneal diameter (HCD) and central corneal thickness (CCT) changes in premature infants with stable optic disc cupping and intraocular pressures (IOPs). The HCD and CCT at term serve as a baseline for premature infants.Sixty-three premature infants were enrolled in a prospective case series. HCD, CCT, and IOP were measured. RetCam images of the optic discs were used to evaluate the cup-disc ratio (CDR) and read by an independent masked observer. Data were collected at between preterm (32-36 weeks) and again at term (37-41 weeks) postconceptual age. Left eye measurements were used for statistical analysis. Left eye findings were combined to construct predictive models for HCD and CCT.The mean HCD was 9.1 mm (standard deviation [SD] = 0.7 mm) at preterm and 10.0 mm (SD = 0.52 mm) at term. The mean CCT preterm was 618.8 (SD = 72.9) μm and at term 563.9 (SD = 50.7) μm, respectively. The average preterm CDR was 0.31 and at maturity was 0.33. Average IOP of preterm and term was 13.1 and 14.11 mm Hg, respectively. There was significant linear correlation between HCD with the postmenstrual age (r = 0.40, P 
  13. Choo MM, Grigg J, Barnes EH, Khaliddin N, Kamalden TA, Ahmad Kamar A, et al.
    BMJ Open Ophthalmol, 2021;6(1):e000626.
    PMID: 33768163 DOI: 10.1136/bmjophth-2020-000626
    Objective: An ongoing third epidemic of retinopathy of prematurity (ROP) is contributed largely by developing nations. We describe a cohort of infants in a single neonatal unit where two limits of oxygen saturation were administered, to show real-world outcomes from trend in neonatology for higher oxygen to improve survival.

    Methods and analysis: This retrospective, comparative study of prospectively collected data in an ROP screening programme included infants indicated by gestational age ≤32 weeks, birth weight <1501 g, ventilation for 7 days or requiring oxygen >1 month, who underwent dilated fundoscopic examination from age 4 weeks, every 2 weeks until full retinal vascularisation. Infants with ROP were examined weekly and treated where indicated. Data were divided into two epochs. Epoch 1 oxygen saturation targets were [88-92%], epoch 2 targets [90-95% (99%)] with allowance of increase to 20% for several hours after procedures. Outcome measures included development of ROP, treatment, mortality, sepsis and intraventricular haemorrhage.

    Results: A total of 651 infants underwent examination between 2003 and 2016. The incidence of ROP in epoch 1 was 29.1% and epoch 2 was 29.3% (p=0.24). ROP progression doubled in epoch 2 (5 vs 11%, p=0.006), proportion of cases treated halved (14% vs 6%, p=0.0005), sepsis was halved (78.5% vs 41.2%, p<0.0001) and intraventricular haemorrhage doubled (20.2% vs 43.8%, p=0.0001) in epoch 2. Mortality was 4% and 0% in epochs 1 and 2, respectively.

    Conclusion: Incidence of ROP did not differ, although ROP cases that worsened doubled with higher oxygen targets. ROP cases requiring treatment decreased, as did sepsis and mortality. Intraventricular haemorrhage cases doubled.

  14. Rafique Ali AA, Ismail F, May May C, Mohd Abdullah AA, Khaliddin N, Hariri F, et al.
    Eur J Ophthalmol, 2021 Jul 05.
    PMID: 34219491 DOI: 10.1177/11206721211030093
    BACKGROUND: This study aims to collect local Malaysian data regarding the ophthalmic features and complications in craniosynostosis patients who attended the Combined Craniofacial Clinic (CFC) in University Malaya Medical Centre (UMMC).

    METHODS: Retrospective study of medical notes of craniosynostosis patients who attended the CFC in UMMC from 2014 to December 2020.

    RESULTS: Out of 37 patients, 29 had syndromic craniosynostosis, and 8 had non-syndromic craniosynostosis. Visual impairment was present in 32.1% of patients. Causes for visual impairment were as follows - amblyopia (25.0%), exposure keratopathy (3.6%), and optic atrophy (3.6%). Hypermetropia and myopia were each seen in 20.6% of patients. Astigmatism was seen in 47.1% of patients, and 29.1% had anisometropia. Proptosis was present in 78.6% and lagophthalmos in 53.3% of patients. Strabismus in primary position occurred in 51.7% of patients. Thirty-one percent of the patients had exposure keratopathy. Optic disc atrophy was seen in 13.7% of patients, and 8.3% had optic disc swelling. Optic disc swelling was resolved in all patients who underwent craniofacial surgery.

    CONCLUSION: Our experience in Malaysia was consistent with previously reported data on ophthalmic features of craniosynostosis patients. Additionally, we found that non-syndromic craniosynostosis patients are also at risk of ocular complications just as much as syndromic patients. Appropriate treatment of amblyogenic risk factors, ocular complications, and timely detection of papilledema, and prompt surgical intervention are crucial in preserving long-term visual function in these patients.

  15. Hariri F, Farhana NA, Abdullah NA, Ibrahim N, Ramli NM, Mohd Abdullah AA, et al.
    J Craniomaxillofac Surg, 2021 Dec;49(12):1175-1181.
    PMID: 34247917 DOI: 10.1016/j.jcms.2021.06.017
    The aim of this study was to compare optic canal parameters of syndromic craniosynostosis patients with those of normal patients to visit the possibility of optic nerve impingement as a cause of visual impairment. Computed tomography scan images were processed using the Materialise Interactive Medical Image Control System (MIMICS) Research 21.0 software (Materialise NV, Leuven, Belgium). Eleven optic canal parameters were measured: 1) height of optic canal on the cranial side, 2) height of optic canal on the orbital side 3) length of the medial wall of the optic canal, 4) length of the lateral canal wall of the optic canal, 5) diameter of the optic canal at five points (Q1-Q4 and mid canal), and 6) area and perimeter of optic canal. These measurements were obtained for both the right and left optic canals. The study sample comprised four Crouzon syndrome, five Apert syndrome, and three Pfeiffer syndrome patients. The age of these syndromic craniosynostosis patients ranged from 2 to 63 months. The height of the optic canal on the orbital side (p = 0.041), diameter of the mid canal (p = 0.040), and diameter between the mid-canal and the cranial opening (Q3) (p = 0.079) for syndromic craniosynostosis patients were statistically narrower compared with those of normal patients when a significance level of 0.1 was considered. Scatter plots for the ages of patients versus the above parameters gave three separated clusters that suggested the arresting of optic canal development with age. The findings from this study demonstrated a narrowing of the optic canal in syndromic craniosynostosis patients, and indicate that optic canal anatomical characteristics may have an association with visual impairment among pediatric syndromic craniosynostosis patients.
  16. Kamalden TA, Macgregor-Das AM, Kannan SM, Dunkerly-Eyring B, Khaliddin N, Xu Z, et al.
    Antioxid Redox Signal, 2017 Nov 01;27(13):913-930.
    PMID: 28173719 DOI: 10.1089/ars.2016.6844
    AIMS: MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.

    RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.

    INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.

    CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.

  17. Hariri F, Abdullah MF, Adam KBC, Bahuri NFA, Kulasegarah J, Nathan AM, et al.
    Int J Oral Maxillofac Surg, 2021 Apr;50(4):457-462.
    PMID: 32891466 DOI: 10.1016/j.ijom.2020.08.002
    Paediatric craniomaxillofacial (CMF) surgery requires a multidisciplinary team approach to ensure the optimal and holistic management of children with craniofacial deformities. The aim of this retrospective study was to analyse the complications following functional interventions among 34 CMF deformity patients in a single multidisciplinary craniofacial centre. Electronic data including patient demographic characteristics and clinical entry were analysed. Inclusion criteria were all paediatric patients with CMF deformities who underwent various functional interventions. A total of 64 interventions (48 intermediate and 16 definitive) were conducted. Based on the Sharma classification of complications, 20.3% were type I, 4.7% were type II, 1.6% were type III, and 4.7% were type IV . Most complications were type I, which included local infection (3.1%) and premature opening of tarsorrhaphy (3.1%). More serious complications (types III and IV) included temporary visual loss (1.6%) and intraoperative haemorrhage (1.6%). Although a low complication rate was observed in intermediate interventions, a higher complication rate was observed in more complex definitive interventions such as monobloc distraction osteogenesis. Although most complications were manageable, effective prevention remains mandatory, as serious complications may lead to permanent damage and mortality. This analysis highlights the importance of a multidisciplinary team approach to optimize the outcomes in CMF patient management.
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