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  1. Nadarajah G, Ratnalingam VH, Mohd Isa H
    Cornea, 2017 Apr;36(4):452-456.
    PMID: 27941383 DOI: 10.1097/ICO.0000000000001106
    PURPOSE: To evaluate graft stability and recurrence rate between fibrin glue and autologous blood in pterygium conjunctival autograft surgery.

    METHODS: A prospective, randomized, single-blinded clinical trial to assess the efficacy of autologous blood in place of fibrin glue in pterygium surgery. A total of 120 eyes of 111 patients were randomized according to pterygium morphology, to undergo pterygium surgery with autografting using either autologous blood or fibrin glue. All patients were operated by a single surgeon; 58 eyes were operated using fibrin glue and 62 eyes had a conjunctival autograft with autologous blood. Patients were seen on postoperative day 1, 1 week, 1 month, 6 months, and 1 year after surgery. Graft stability and pterygium recurrence were graded by an independent observer who was masked to the method of treatment.

    RESULTS: All 120 eyes completed the 1-year follow-up. Graft loss was seen only in the autologous blood group. Of the 62 eyes in this group, a total of 15 (24.2%) grafts dislodged. Recurrence was calculated after excluding grafts that were dislodged. Of the 105 patients, there were a total of 7 recurrences, 2 (3.4%) from the fibrin adhesive method and 5 (10.6%) from the autologous blood method. This was not statistically significant (P = 0.238).

    CONCLUSIONS: Autologous blood does not exhibit similar graft stability seen with fibrin glue. Although the recurrence rate may not be significant, careful patient selection and a standard method needs to be laid out before the use of this method is widely accepted.

  2. Din NM, Taylor SR, Isa H, Tomkins-Netzer O, Bar A, Talat L, et al.
    JAMA Ophthalmol, 2014 Jul;132(7):859-65.
    PMID: 24789528 DOI: 10.1001/jamaophthalmol.2014.404
    IMPORTANCE: Uveitic glaucoma is among the most common causes of irreversible visual loss in uveitis. However, glaucoma detection can be obscured by inflammatory changes.

    OBJECTIVE: To determine whether retinal nerve fiber layer (RNFL) measurement can be used to detect glaucoma in uveitic eyes with elevated intraocular pressure (IOP).

    DESIGN, SETTING, AND PARTICIPANTS: Comparative case series of RNFL measurement using optical coherence tomography performed from May 1, 2010, through October 31, 2012, at a tertiary referral center. We assigned 536 eyes with uveitis (309 patients) in the following groups: normal contralateral eyes with unilateral uveitis (n = 72), normotensive uveitis (Uv-N) (n = 143), raised IOP and normal optic disc and/or visual field (Uv-H) (n = 233), and raised IOP and glaucomatous disc and/or visual field (Uv-G) (n = 88).

    EXPOSURES: Eyes with uveitis and elevated IOP (>21 mm Hg) on at least 2 occasions.

    MAIN OUTCOMES AND MEASURES: Comparison of RNFL values between groups of eyes and correlation with clinical data; risk factors for raised IOP, glaucoma, and RNFL thinning.

    RESULTS: Mean (SD) global RNFL was thicker in Uv-N (106.4 [21.4] µm) compared with control (96.0 [9.0] µm; P H eyes with no evidence of disc or visual field changes (P = .03). Risk factors for elevated IOP were male sex and anterior uveitis. Age, higher peak IOP, longer duration of follow-up, and uveitis-induced elevation of IOP were risk factors for glaucoma and RNFL defect.

    CONCLUSIONS AND RELEVANCE: Screening for glaucomatous RNFL changes in uveitis must be performed during quiescent periods. Thinning of the inferior quadrant suggests that glaucomatous damage, more than uveitic ocular hypertension, is in fact occurring. Measurement of RNFL may detect signs of damage before disc or visual field changes and therefore identifies a subgroup that should receive more aggressive treatment.

  3. Tan LT, Davagnanam I, Isa H, Rose GE, Verity DH, Pusey CD, et al.
    Ophthalmology, 2015 Oct;122(10):2125-9.
    PMID: 26233627 DOI: 10.1016/j.ophtha.2015.06.026
    Lacrimal gland involvement in granulomatosis with polyangiitis (GPA) commonly accompanies orbital disease, but occasionally may be the sole presentation preceding any other organ manifestation or systemic disease. Diagnosis of orbital GPA, especially in patients with lacrimal involvement as the initial presentation, can be difficult because of nonspecific clinical features and lack of diagnostic specificity on histologic and antineutrophilic cytoplasmic antibody (ANCA) testing. Orbital GPA can be associated with a high morbidity from potential visual loss or rapid progression of latent systemic disease, making early diagnosis important. The purpose of this study was to describe the clinical and imaging features of patients with lacrimal gland involvement secondary to GPA and to compare them with those of other orbital inflammatory conditions in the lacrimal gland fossa.
  4. Md Din N, Tomkins-Netzer O, Talat L, Taylor SR, Isa H, Bar A, et al.
    J Glaucoma, 2016 07;25(7):598-604.
    PMID: 26900824 DOI: 10.1097/IJG.0000000000000379
    PURPOSE: To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness.

    PATIENTS AND METHODS: Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP.

    RESULTS: IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 μm) compared with NU eyes (142.1±32.0 μm, P=0.043).

    CONCLUSIONS: Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

    Study site: Moorfields Eye Hospital, London
  5. Din NM, Talat L, Isa H, Tomkins-Netzer O, Barton K, Lightman S
    Graefes Arch Clin Exp Ophthalmol, 2016 Dec;254(12):2439-2448.
    PMID: 27495303
    PURPOSE: To determine whether the second eyes (SE) of patients with bilateral uveitic glaucoma undergoing filtration surgery have more glaucomatous progression in terms of visual acuity, visual field (VF) and optic nerve changes compared to the first eyes (FE).

    METHODS: This retrospective study analysed data of 60 eyes from 30 patients with bilateral uveitic glaucoma who had undergone glaucoma surgery in both eyes on separate occasions. Humphrey VF progression was assessed using the Progressor software.

    RESULTS: The pre-operative IOP between the FE (43.1 ± 7.7 mmHg) and SE (40 ± 8.7 mmHg) was not statistically significant (p = 0.15). IOP reduction was greater in the FE (64 %) than SE (59.7 %) post-operatively, but the mean IOP at the final visit in the FE (12.3 ± 3.9 mmHg) and SE (14.5 ± 7 mmHg) was not statistically different (p = 0.2). There was no significant change in mean logMAR readings pre and post-operatively (0.45 ± 0.6 vs 0.37 ± 0.6, p = 0.4) or between the FE and SE. The number of SE with CDR > 0.7 increased by 23 % compared to the FE. From 23 available VFs, five SE (21.7 %) progressed at a median of five locations (range 1-11 points) with a mean local slope reduction of 1.74 ± 0.45 dB/year (range -2.39 to -1.26), whereas only one FE progressed. However, there was no significant difference between mean global rate of progression between the FE (-0.9 ± 1.6 dB/year) and SE (-0.76 ± 2.1 dB/year, p = 0.17) in the Humphrey VF.

    CONCLUSION: In eyes with bilateral uveitic glaucoma requiring glaucoma surgery, the SEs had more progressed points on VF and glaucomatous disc progression compared to FEs at the final visit.

  6. Loh CC, Kamaruddin H, Bastion MC, Husain R, Mohd Isa H, Md Din N
    Ophthalmic Res, 2021;64(2):246-252.
    PMID: 32810853 DOI: 10.1159/000510925
    INTRODUCTION: The aim of the study was to evaluate the refractive status and ocular biometric parameters in subjects with angle closure in Malaysia.

    METHODS: This cross-sectional study was conducted on 171 primary angle closure patients (268 eyes). Visual acuity, refraction, and ocular biometry (central anterior chamber depth [ACD], axial length [AL], and lens thickness) were recorded. Vitreous cavity length (VL) and relative lens position (RLP) were calculated.

    RESULTS: A total of 92 Primary Angle Closure Suspect (PACS), 30 Primary Angle Closure (PAC), and 146 Primary Angle Closure Glaucoma (PACG) eyes were included. Chinese ethnicity formed the majority (n = 197, 73.5%), followed by Malay (n = 57, 21.3%) and Indian (n = 14, 5.2%). There was a significant female preponderance with a female to male ratio of 1.85. Mean age was 65.7 ± 7.7 years. Mean spherical equivalent was +0.33 ± 1.29 D. Approximately half (n = 137, 51%) of the eyes were hyperopic (spherical power ≥+0.5), with PACG having the highest percentage of hyperopia (n = 69, 50.4%). Myopia and emmetropia were present in 48 (17.9) and 83 (31%) eyes, respectively. Although AL and VL in myopia patients were significantly longer than emmetropic and hyperopic eyes (p < 0.001), the ACD was not significantly different (p = 0.427). While the RLP is smaller in myopic eyes, lens thickness was increased in hyperopic eyes. PACG was significantly higher in elderly patients compared to PACS and PAC (p = 0.005). A total of 37 (13.8%) eyes were blind (vision worse than 3/60) and 19 of them (51.3%) were female patients.

    CONCLUSION: A decrease in RLP is predictive of angle closure disease in myopic eyes, whereas increased lens thickness contributes to angle closure disease in hyperopic eyes.

  7. Mustapha M, Abdollah Z, Ahem A, Mohd Isa H, Bastion MC, Din NM
    Int J Ophthalmol, 2018;11(9):1573-1576.
    PMID: 30225238 DOI: 10.18240/ijo.2018.09.25
  8. Tan LT, Davagnanam I, Isa H, Taylor SR, Rose GE, Verity DH, et al.
    Ophthalmology, 2014 Jun;121(6):1304-9.
    PMID: 24560566 DOI: 10.1016/j.ophtha.2013.12.003
    Granulomatosis with polyangiitis (GPA), previously Wegener's granulomatosis, requires prompt diagnosis and systemic review to exclude life-threatening disease. However, early diagnosis of orbital GPA may be difficult because anti-neutrophil cytoplasmic antibody (ANCA) and anti-PR3 antibody screening can be negative at presentation and orbital biopsies taken for diagnosis may not show the classic features of GPA. This study was designed to compare GPA with other causes of orbital inflammation and to identify the presenting clinical and imaging features most likely to predict GPA and its systemic spread.
  9. Suwarnalata G, Tan AH, Isa H, Gudimella R, Anwar A, Loke MF, et al.
    PLoS One, 2016;11(4):e0153725.
    PMID: 27100827 DOI: 10.1371/journal.pone.0153725
    Parkinson's disease (PD) is the second most common chronic and progressive neurodegenerative disorder. Its etiology remains elusive and at present only symptomatic treatments exists. Helicobacter pylori chronically colonizes the gastric mucosa of more than half of the global human population. Interestingly, H. pylori positivity has been found to be associated with greater of PD motor severity. In order to investigate the underlying cause of this association, the Sengenics Immunome protein array, which enables simultaneous screening for autoantibodies against 1636 human proteins, was used to screen the serum of 30 H. pylori-seropositive PD patients (case) and 30 age- and gender-matched H. pylori-seronegative PD patients (control) in this study. In total, 13 significant autoantibodies were identified and ranked, with 8 up-regulated and 5 down-regulated in the case group. Among autoantibodies found to be elevated in H. pylori-seropositive PD were included antibodies that recognize Nuclear factor I subtype A (NFIA), Platelet-derived growth factor B (PDGFB) and Eukaryotic translation initiation factor 4A3 (eIFA3). The presence of elevated autoantibodies against proteins essential for normal neurological functions suggest that immunomodulatory properties of H. pylori may explain the association between H. pylori positivity and greater PD motor severity.
  10. Yahya P, Sulong S, Harun A, Wan Isa H, Ab Rajab NS, Wangkumhang P, et al.
    Forensic Sci Int Genet, 2017 09;30:152-159.
    PMID: 28743033 DOI: 10.1016/j.fsigen.2017.07.005
    Malay, the main ethnic group in Peninsular Malaysia, is represented by various sub-ethnic groups such as Melayu Banjar, Melayu Bugis, Melayu Champa, Melayu Java, Melayu Kedah Melayu Kelantan, Melayu Minang and Melayu Patani. Using data retrieved from the MyHVP (Malaysian Human Variome Project) database, a total of 135 individuals from these sub-ethnic groups were profiled using the Affymetrix GeneChip Mapping Xba 50-K single nucleotide polymorphism (SNP) array to identify SNPs that were ancestry-informative markers (AIMs) for Malays of Peninsular Malaysia. Prior to selecting the AIMs, the genetic structure of Malays was explored with reference to 11 other populations obtained from the Pan-Asian SNP Consortium database using principal component analysis (PCA) and ADMIXTURE. Iterative pruning principal component analysis (ipPCA) was further used to identify sub-groups of Malays. Subsequently, we constructed an AIMs panel for Malays using the informativeness for assignment (In) of genetic markers, and the K-nearest neighbor classifier (KNN) was used to teach the classification models. A model of 250 SNPs ranked by In, correctly classified Malay individuals with an accuracy of up to 90%. The identified panel of SNPs could be utilized as a panel of AIMs to ascertain the specific ancestry of Malays, which may be useful in disease association studies, biomedical research or forensic investigation purposes.
  11. Isa H, Luthert P, Rose G, Verity D, Pusey C, Tomkins-Netzer O, et al.
    Ophthalmology, 2015 Oct;122(10):2140-2.
    PMID: 26116342 DOI: 10.1016/j.ophtha.2015.04.016
  12. Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.
    Bosn J Basic Med Sci, 2018 Aug 01;18(3):260-267.
    PMID: 29579408 DOI: 10.17305/bjbms.2018.2493
    Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.
  13. Bakri NM, Ramachandran V, Kee HF, Subrayan V, Isa H, Ngah NF, et al.
    Kaohsiung J. Med. Sci., 2017 Dec;33(12):602-608.
    PMID: 29132549 DOI: 10.1016/j.kjms.2017.08.003
    Age-related macular degeneration (AMD) is the most widely recognised cause of irreversible vision loss and previous studies have suggested that the advancement of wet AMD is influenced by both modifiable and non-modifiable elements. Single nucleotide polymorphism (SNPs) and copy number of variations (CNVs) have been associated with AMD in various populations, however the results are conflicting. Our aim is to determine the CNVs of Complement Factor H-Related genes among Malaysian subjects with wet AMD. 130 patients with wet AMD and 120 healthy controls were included in this research. DNA was extracted from all subjects and CNVs of CFH, CFHR1 and CFHR3 genes; determined using quantitative real-time PCR and were compared between the two groups. A consistent association was observed between CFH gene and wet AMD susceptibility (P 
  14. Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.
    Genet Test Mol Biomarkers, 2017 Oct;21(10):600-607.
    PMID: 28926292 DOI: 10.1089/gtmb.2017.0079
    AIM: To determine the association of vascular endothelial growth factor (VEGF) polymorphisms with neovascular age-related macular degeneration (nAMD).

    MATERIALS AND METHODS: One hundred thirty-five nAMD patients and 135 controls were recruited to determine the association of the -460 C/T, the -2549 I/D, and the +405 G/C polymorphisms with the VEGF gene. Genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, and association analyses were conducted using chi-square analysis and logistic regression analysis.

    RESULTS: A significant association was observed between nAMD and the VEGF +405 G/C genotypes (p = 0.002) and alleles (odds ratio = 1.36, 95% confidence interval = 1.12-1.62, p = < 0.001) compared with the controls. This association was confirmed by logistic regression analyses, using two different genetic models (additive and dominant) resulting in p-values of p = 0.001 and p 

  15. Mohamad NA, Ramachandran V, Mohd Isa H, Chan YM, Ngah NF, Ching SM, et al.
    Hum Genomics, 2019 02 22;13(1):13.
    PMID: 30795802 DOI: 10.1186/s40246-019-0197-3
    BACKGROUND: The association of HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms with response to intravitreal ranibizumab therapy among neovascular AMD (nAMD) subjects in Malaysia was determined in this study, followed by the expression of HTRA1 and ARMS2 genes.

    RESULTS: Both single nucleotide polymorphisms (SNPs) recorded a significant association between nAMD and controls with HTRA1 rs11200638 at P = 0.018 (OR = 1.52, 95% CI = 1.07-215) and ARMS2 rs10490924 at P 

  16. Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.
    Int J Ophthalmol, 2017;10(12):1889-1897.
    PMID: 29259909 DOI: 10.18240/ijo.2017.12.16
    AIM: To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy (PDT) among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014.

    METHODS: Study subjects were recruited retrospectively using the Electronic Medical Record (EMR) database software in Hospital Selayang. Demographic data, medical history, diagnostic procedure, treatments and diagnosis of patients were recorded.

    RESULTS: The five-year analysis included 821 patients with a mean age of 65.9±11.73y. Overall, there were a higher number of males (63.1%) and a higher number of Chinese (47.4%) patients. Among the 821 patients, 62.9% received ranibizumab injection followed by 19.2% PDT therapy and 17.9% had ranibizumab combined with PDT therapy. Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) were the most common retinal eye diseases reported, recording prevalence of 25.0% and 45.6%, respectively. The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014. In terms of treatment, following multiple logistic regression, AMD was associated with the subjects being more likely to have received ranibizumab monotherapy (P<0.001) while PCV was associated with more likely to have received PDT (P<0.001) and PDT combined with ranibizumab therapy (P<0.001).

    CONCLUSION: The tertiary care setting in Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD, while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.

    Study site: Ophthalmology Clinic, Hospital Selayang
  17. Koh AE, Alsaeedi HA, Rashid MBA, Lam C, Harun MHN, Ng MH, et al.
    Front Cell Dev Biol, 2021;9:652017.
    PMID: 33987180 DOI: 10.3389/fcell.2021.652017
    Mesenchymal stem cells (MSC) are highly regarded as a potential treatment for retinal degenerative disorders like retinitis pigmentosa and age-related macular degeneration. However, donor cell heterogeneity and inconsistent protocols for transplantation have led to varied outcomes in clinical trials. We previously showed that genetically-modifying MSCs to express erythropoietin (MSCEPO) improved its regenerative capabilities in vitro. Hence, in this study, we sought to prove its potential in vivo by transplanting MSCsEPO in a rat retinal degeneration model and analyzing its retinal transcriptome using RNA-Seq. Firstly, MSCsEPO were cultured and expanded before being intravitreally transplanted into the sodium iodate-induced model. After the procedure, electroretinography (ERG) was performed bi-weekly for 30 days. Histological analyses were performed after the ERG assessment. The retina was then harvested for RNA extraction. After mRNA-enrichment and library preparation, paired-end RNA-Seq was performed. Salmon and DESeq2 were used to process the output files. The generated dataset was then analyzed using over-representation (ORA), functional enrichment (GSEA), and pathway topology analysis tools (SPIA) to identify enrichment of key pathways in the experimental groups. The results showed that the MSCEPO-treated group had detectable ERG waves (P <0.05), which were indicative of successful phototransduction. The stem cells were also successfully detected by immunohistochemistry 30 days after intravitreal transplantation. An initial over-representation analysis revealed a snapshot of immune-related pathways in all the groups but was mainly overexpressed in the MSC group. A subsequent GSEA and SPIA analysis later revealed enrichment in a large number of biological processes including phototransduction, regeneration, and cell death (P adj <0.05). Based on these pathways, a set of pro-survival gene expressions were extracted and tabulated. This study provided an in-depth transcriptomic analysis on the MSCEPO-treated retinal degeneration model as well as a profile of pro-survival genes that can be used as candidates for further genetic enhancement studies on stem cells.
  18. Halim-Fikri H, Etemad A, Abdul Latif AZ, Merican AF, Baig AA, Annuar AA, et al.
    BMC Res Notes, 2015;8:176.
    PMID: 25925844 DOI: 10.1186/s13104-015-1123-y
    The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb).
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