Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Modified Four-Point Scleral Fixated Sutured Posterior Chamber Intraocular Lens Implantation Using 2 Eyelets Polymethyl Methacrylate Lens and 8-0 Polypropylene Suture.

Purpose: To present a modified technique of 4-point scleral fixation using polymethyl methacrylate (PMMA) 2 eyelets intraocular lens (IOL) with 8-0 polypropylene sutures. Methods: A 270-degree conjunctival peritomy is done, and 4 sclerotomies (2 nasal and 2 temporal) are created. Lamellar scleral or clear corneal incision is made at superior site (6 mm wide for sclera or 5.5-6 mm for corneal). A short segment of 8-0 polypropylene is inserted into each eyelet, each thread of the suture is externalized through the sclerotomy site, and the lens is inserted. The suture is tightened evenly, and the knot is rotated and internalized. Scleral incision and conjunctival peritomy are sutured with 8-0 vicryl. Results: We have performed this technique in 6 patients with excellent visual outcomes and no reported complications over 1 year of follow-up. This technique has practical advantages including rigid and stable PMMA IOL, high tensile, and slim 8-0 polypropylene suture which is easily internalized and less irritated, and affordable and widely available overall consumables. Conclusion: We present a modified 4-point scleral fixation technique for posterior chamber IOL placement using PMMA IOL with 2 eyelets and 8-0 polypropylene as compared to previous studies that used foldable IOL with 4 eyelets and 10-0 polypropylene or Gore-Tex sutures. This procedure has moderate technical complexity, comparable to previously reported techniques with good overall clinical outcomes and several practical advantages, particularly related to the affordability and availability of the consumables.

Serum apolipoprotein A1 and B are associated with 6-month persistent and incident diabetic macular oedema in type 2 diabetes.

AIMS: To investigate the associations of baseline apolipoprotein A1 (ApoA1) and B (ApoB) levels with persistent and incident diabetic macular oedema (DMO) after 6 months of follow-up. METHODS: This is a prospective cohort study of patients aged ≥30 years with untreated diabetic retinopathy. Examinations, fundus photography and spectral domain optical coherence tomography (SD-OCT) were assessed at baseline, 1, 3 and 6 months. Serum lipids and apolipoproteins were analysed at a pathology laboratory. DMO was confirmed using SD-OCT, classified as (1) incident DMO, (2) persistent DMO and (3) regressed DMO. Eye-specific data were used, controlling for covariates and cluster effect. RESULTS: We recruited 53 patients but only 38 completed the study [(62 eyes), 20 eyes (32.3%) with DMO]. Higher quartile of ApoA1 was associated with lower risk of persistent/incident DMO (p for trend 0.02), while higher ApoB/A1 was associated with higher risk of persistent/incident DMO (p for trend 0.02). Every 10 mg/dL increase in ApoA1 levels was associated with lower risk of persistent/incident DMO (OR 0.69; 95% CI 0.49 to 0.92; p value 0.016), whereas every 0.2 increase in ApoB/A1 was significantly associated with higher risk of persistent/incident DMO (OR 1.4; 95% CI 1.1 to 1.9; p value 0.013) at the end of the study. CONCLUSION: Individuals with diabetes with higher ApoA1 had lower risk of persistent/incident DMO and those with higher ApoB/A1 had higher risk of persistent/incident DMO at the end of 6 months. These suggest that serum ApoA1 and ApoB/A1 levels may be important risk factors for DMO and could be predictive of persistent/incident DMO despite anti-vascular endothelial growth factor treatment.

Accuracy of Low-Cost, Smartphone-Based Retinal Photography for Diabetic Retinopathy Screening: A Systematic Review.

Purpose: Diabetic retinopathy (DR) is a leading cause of blindness. Early DR screening is essential, but the infrastructure can be less affordable in low resource countries. This study aims to review the accuracy of low-cost smartphone-based fundus cameras for DR screening in adult patients with diabetes. Methods: We performed a systematic literature search to find studies that reported the sensitivity and specificity of low-cost smartphone-based devices for fundus photography in adult patients with diabetes. We searched three databases (MEDLINE, Google Scholar, Scopus) and one register (Cochrane CENTRAL). We presented the accuracy values by grouping the diagnosis into three: any DR, referrable DR, and diabetic macular oedema (DMO). Risk of bias and applicability of the studies were assessed using QUADAS-2. Results: Five out of 294 retrieved records were included with a total of six smartphone-based devices reviewed. All of the reference diagnostic methods used in the included studies were either indirect ophthalmoscopy or slit-lamp examinations and all smartphone-based devices' imaging protocols used mydriatic drops. The reported sensitivity and specificity for any DR were 52-92.2% and 73.3-99%; for referral DR were 21-91.4% and 64.9-100%; and for DMO were 29.4-81% and 95-100%, respectively. Conclusion: Sensitivity available low-cost smartphone-based devices for DR screening were acceptable and their specificity particularly for detecting referrable DR and DMO were considerably good. These findings support their potential utilization for DR screening in a low resources setting.

Modifiable lifestyle and environmental risk factors affecting the retinal microcirculation.

Structural changes within the human retinal vasculature may reflect systemic vascular changes associated with various cardiovascular and metabolic disorders. Recent data suggest that systemic exposure from a range of modifiable lifestyle and environmental risk factors (e.g., diet, physical activity, and smoking) may affect the morphology of the retinal vasculature. Being easily accessible and non-invasively visualized, the retinal microvasculature therefore can be a clinically useful biomarker of reversible sub-clinical physiologic deviation of the systemic circulation as results of such unfavorable exposures. Importantly, quantitative analysis of the retinal microvasculature may be utilized as a prognostic tool, allowing for targeted vascular therapies before the onset of overt cardiovascular and metabolic disorders. This review summarizes the modifiable lifestyle and environmental risk factors that affect retinal microvascular structure and the possible clinical implications of such relationships.

Longer axial length is protective of diabetic retinopathy and macular edema.

PURPOSE: To assess the association of ocular biometric parameters and refractive error with diabetic retinopathy (DR) and diabetic macular edema (DME) in persons with diabetes. DESIGN: Cross-sectional, clinic-based study. PARTICIPANTS: Patients with diabetes aged 18 years or more from the Royal Victorian Eye and Ear Hospital, Victoria, Australia. METHODS: Spherical equivalent (SE) refraction was assessed using objective autorefraction. Axial length (AL), corneal curvature (CC), and anterior chamber depth (ACD) were measured using the IOLMaster (Carl Zeiss Meditech AG, Jena, Germany). Diabetic retinopathy was graded from 2-field retinal photographs using the modified Airlie House classification system. Diabetic macular edema was defined as absent or present from fundus photographs and confirmed by optical coherence tomography (Stratus, Carl Zeiss Meditech AG). MAIN OUTCOME MEASURES: Severity of DR was grouped as no DR, mild DR (Early Treatment of Diabetic Retinopathy Study [ETDRS] = 20), moderate DR (ETDRS = 31-43), and severe DR (ETDRS >43). Diabetic macular edema severity was classified as mild, moderate, or severe. RESULTS: A total of 208 of 630 eyes (33.0%) had DR. In multivariate models, eyes with longer AL were less likely to have mild (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.41-0.83; P = 0.006 per mm increase), moderate (OR, 0.73; 95% CI, 0.60-0.88; P = 0.002), and severe DR (OR, 0.67; 95% CI, 0.53-0.85; P=0.01), and had a lesser risk of mild (OR, 0.70; 95% CI, 0.56-0.86; P < 0.001) and moderate DME (OR, 0.72; 95% CI, 0.56-0.93; P=0.002) but not severe DME. No association was found for SE, ACD, and CC with DR. CONCLUSIONS: In persons with diabetes, eyes with longer ALs are less likely to have DR and DME.

Large, star-shaped retinal tear associated with orbital cosmetic filler.

PURPOSE: Presentation of a unique case of large, star-shaped retinal tear associated with orbital cosmetic filler injection. OBSERVATION: A 55-year-old healthy female presented to emergency department with sudden onset of blurred vision on her left eye occurred after an orbital cosmetic filler injection containing hyaluronic acid (HA) performed by an aesthetic nurse. On fundus examination, the left eye showed a mild - moderate, unusual appearance vitreous haze and a large, star-shaped retinal tear temporal to macula. Optical coherence tomography (OCT) examination demonstrated a normal foveal contour without any structural damage on the retinal layers. Vitrectomy, endolaser and silicon oil tamponade were performed. Visual acuity was maintained at 6/7.5 following silicon oil removal at 6 weeks after the initial surgery. CONCLUSIONS AND IMPORTANCE: In this particular case, immediate vitrectomy is key to avoid further complications such as retinal toxicity and detachment and to maintain optimal visual acuity. Importantly, facial cosmetic filler procedure should be performed by an adequately trained individual to avoid such complications.

A Novel Biomarker in Primary Glaucoma: Aqueous Humor and Serum Levels of Ischemia Modified Albumin (IMA).

Purpose: To analyze ischemia-modified albumin (IMA) levels in aqueous humor and serum, and their correlation to RNFL thinning in primary glaucoma patients. Design: Cross-sectional study. Methods: Patients were divided into the control and glaucoma groups. The control group was patients with senile cataracts. The glaucoma group consisted of patients diagnosed for the first time as primary open-angle glaucoma (POAG) or primary angle closure glaucoma (PACG). Exclusion criteria were secondary glaucoma and patients with systemic disease. A complete cataract examination was done for all patients, and glaucoma examinations for the glaucoma group. In both groups, the IMA aqueous humor was obtained during cataract and glaucoma procedure. Serum levels of IMA, malondialdehyde (MDA), and tumor necrosis factor alpha (TNF-α) were examined during preoperative examinations. Results: Control group comprised 33 participants, and glaucoma group 41 patients (21 PACG and 20 POAG). Mean IMA aqueous humor (AQH) levels found in cataract group 6.039±3.16 ng/mL, glaucoma group 14.89±6.08 ng/mL, PACG group 12.69±6.25 ng/mL and POAG group 17.33±4.988 mg/mL. Mean IMA serum levels in cataract group 14.75±6.53 ng/mL, glaucoma group 13.89±6.53 ng/mL, PACG group 12.79±6.46 ng/mL± and POAG group 14.93±10.74 ng/mL. Glaucoma group had significant higher level of IMA in aqueous humor compared to control group, but opposite findings in serum IMA levels between groups. POAG patients had a higher aqueous IMA level compared to PACG group and correlated significantly with IOP. IMA AQH also negatively correlated to the RNFL thickness in both POAG and PACG group. Cut off 9.5 ng/mL was considered as a normal limit value to differentiate between control and glaucoma group. Conclusion: Primary glaucoma patients showed a significantly increased level of IMA AQH as a local ischemic biomarker compared to the control group. Systemic oxidative activity is not a representation of local ocular oxidative stress in both cataract and glaucoma group.

Efficient and Robust Method to Detect the Location of Macular Center Based on Optimal Temporal Determination.

The location of the macular central is very important for the examination of macular edema when using an automated screening system. The erratic character of the macular light intensity and the absence of a clear border make this anatomical structure difficult to detect. This paper presents a new method for detecting the macular center based on its geometrical location in the temporal direction of the optic disc. Also, a new method of determining the temporal direction using the vascular features visible on the optic disc is proposed. After detecting the optic disc, the temporal direction is determined by considering blood vessel positions. The macular center is detected using thresholding and simple morphology operations with optimum macular region of interest (ROI) direction. The results show that the proposed method has a low computation time of 0.34 s/image with 100% accuracy for the DRIVE dataset, while that of DiaretDB1 was 0.57 s/image with 98.87% accuracy.

Cholesterols, Apolipoproteins, and Their Associations with the Presence and Severity of Diabetic Retinopathy: A Systematic Review.

Serum apolipoproteins have been reported as a more significant marker for diabetic retinopathy (DR) compared with serum cholesterols. This article aims to review the associations between serum cholesterols and apolipoproteins, and the presence and severity of DR. The protocol of this systematic review was registered at the PROSPERO registry (CRD42022303331). We conducted a systematic search of literature published between 2011 to 2022 using the search terms "serum cholesterol" AND/OR "lipoprotein" AND/OR "apolipoprotein" AND/OR "diabetic retinopathy". Fifteen studies were included in this review. Six studies assessed the association between serum cholesterols, apolipoproteins, and the presence of DR. Three studies reported lower levels of apolipoprotein A1, and one study reported higher levels of apolipoprotein B in patients with DR. The remaining nine studies compared serum cholesterol and apolipoprotein levels according to DR severity. Patients with more severe grades of DR presented with lower apolipoprotein A1 in six (66.7%) studies, higher apolipoprotein B levels in seven (77.8%) studies, and a higher apolipoprotein B/apolipoprotein A1 ratio in six out of seven (85%) studies. In conclusion, serum apolipoproteins, in particular the apolipoprotein B/apolipoprotein A1 ratio, were a more consistent marker for DR severity compared with serum cholesterols.

Prevalence of diabetes in pregnancy and microvascular complications in native Indonesian women: The Jogjakarta diabetic retinopathy initiatives in pregnancy (Jog-DRIP).

OBJECTIVES: To report the prevalence of total diabetes in pregnancy (TDP) and diabetes-related microvascular complications among Indonesian pregnant women. METHODS: We conducted a community-based cross-sectional study with multi-stage, cluster random sampling to select the participating community health centers (CHC) in Jogjakarta, Indonesia between July 2018-November 2019. All pregnant women in any trimester of pregnancy within the designated CHC catchment area were recruited. Capillary fasting blood glucose (FBG) and blood glucose (BG) at 1-hour (1-h), and 2-hour (2-h) post oral glucose tolerance test (OGTT) were measured. TDP was defined as the presence of pre-existing diabetes or diabetes in pregnancy (FBG ≥7.0 mmol/L, or 2-h OGTT ≥11.1 mmol/L, or random BG ≥11.1 mmol/L with diabetes symptoms). Disc and macula-centered retinal photographs were captured to assess diabetic retinopathy (DR). Blood pressure, HbA1c and serum creatinine levels were also measured. RESULTS: A total of 631/664 (95%) eligible pregnant women were included. The median age was 29 (IQR 26-34) years. The prevalence of TDP was 1.1% (95%CI 0.5, 2.3). It was more common in women with chronic hypertension (p = 0.028) and a family history of diabetes (p = 0.015). Among the TDP group, 71% had a high HbA1c, but no DR nor nephropathy were observed. CONCLUSIONS: Although a very low prevalence of TDP and no diabetes-related microvascular complications were documented in this population, there is still a need for a screening program for diabetes in pregnancy. Once diabetes has been identified, appropriate management can then be provided to prevent adverse outcomes.

rs10737680 polymorphism in complement factor H and neovascular age-related macular degeneration in Yogyakarta, Indonesia.

Background: Neovascular age-related macular degeneration (nAMD) is one of the main causes of blindness in developed countries. Complement factor H (CFH) is one of the genes involved in the pathogenesis of nAMD. This study investigated the rs10737680 polymorphism in CFH and its conferred susceptibility to nAMD in Yogyakarta, Indonesia. Methods: This case-control hospital-based study recruited participants consisting of 96 patients with nAMD and 101 controls without nAMD from the Eye Polyclinic of Sardjito Hospital, YAP Eye Hospital, and Hardjolukito Hospital Yogyakarta. nAMD was diagnosed when fundus examination, fundus photographs, and optical coherence tomography revealed hard or soft drusen in the macular area measuring > 63 µm that appeared below the retinal pigment epithelium, with or without macular hypo- or hyperpigmentation, and was accompanied by choroidal neovascularization. Genomic DNA was extracted using a commercial DNA isolation kit. The restriction fragment length polymorphism technique was used to identify the rs10737680 polymorphism in CFH. Results: The mean (standard deviation [SD]) age of the nAMD group was not homogeneous with that of the control group (P < 0.05); 65.41 (9.74) years versus 68.24 (7.82) years. The number of patients with hypertension in the nAMD group was significantly higher than in the control group (P < 0.05). In the nAMD group, the genotype distribution indicated homozygous risk allele in 34.38%, heterozygous risk allele in 57.29%, and homozygous non-risk allele in 8.33%. In the control group, the genotype distribution indicated homozygous risk allele in 21.78%, heterozygous risk allele in 36.63%, and homozygous non-risk allele in 41.58%. Statistical analysis between the two study groups according to homozygous risk allele genotype (odds ratio [OR], 7.87; 95% confidence interval [CI], 2.88-22.79) and heterozygous genotype (OR, 7.80; 95% CI, 3.11-21.19) showed a significant difference (both P < 0.01). Conclusions: Homozygous risk allele was less frequent than heterogeneous risk allele in patients with nAMD; however, both increased the risk for nAMD. Although the homozygous or heterozygous risk-alleles were detected in most patients, yet other important genetic or environmental factors could be involved in the pathogenesis of nAMD. Overall, we found a significant association between rs10737680 polymorphism in CFH and the susceptibility to nAMD in Yogyakarta, Indonesia; however, future studies are needed to fully delineate the mechanism.

Association of the HtrA1 rs11200638 Polymorphism with Neovascular Age-Related Macular Degeneration in Indonesia.

INTRODUCTION: The aim of this study was to investigate the association of the HtrA1 rs11200638 polymorphism with neovascular age-related macular degeneration (nAMD) in Indonesia. METHODS: This case-control study included 80 patients with nAMD and 85 controls. Demographic parameters and whole blood were collected from each participant. Genomic DNA was extracted and used to assess the rs11200638 genotype by PCR and restriction enzyme digestion. Associations between the HtrA1 rs11200638 polymorphism and other risk factors for susceptibility to nAMD were assessed using the logistic regression model. RESULTS: Significant allelic associations between the HtrA1 polymorphism and nAMD were detected (odds ratio [OR] 8.67; 95% confidence interval [CI] 4.88-15.41; P < 0.001). Genotype analysis showed a statistical difference between the nAMD group and the control group (P < 0.001). In the multiple adjusted logistic regression model, people with the AA genotype were more likely to have nAMD although there was a wide confidence interval (OR 19.65; 95% CI 4.52-85.38; P < 0.001). CONCLUSION: Our findings show that the risk of nAMD increased in the presence of risk alleles of HtrA1 rs11200638.

Two-step versus 1-step subretinal injection to compare subretinal drug delivery: a randomised study protocol.

INTRODUCTION: There is increasing interest in subretinal injections as a surgical procedure, largely as a result of emerging treatments for ocular diseases which necessitate this manoeuvre. However, surgical variables in the efficacy of such treatments have to date been largely overlooked and the proportion of drug which reaches the intended compartment of the subretinal space remains unknown. Our aims are twofold: first, to determine the proportion of subretinally injected medication retained following surgical delivery and second, to compare two different techniques of injection ('1-step' vs '2-step'). METHODS: We outline a randomised controlled trial of subretinal injection of alteplase following vitrectomy for the management of submacular haemorrhage secondary to age-related macular degeneration. Patients will be randomised to receive either 1-step injection, where the therapeutic solution simultaneously defines the surgical plane or 2-step injection, where the surgical plane is first identified with balanced salt solution prior to injection of subretinal alteplase, as outlined below. Sodium fluorescein will be used as an optical label to track drug reflux into the vitreous cavity using quantitative protocols established in our laboratory. All patients will undergo fluid air exchange at the completion of surgery, with injection of bevacizumab 1.25 mg and 20% sulfahexafluoride gas as the vitreous substitute (both of which may help improve outcomes). Alteplase, sodium fluorescein and bevacizumab will all be used for off-label indications in the trial. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South Eastern Sydney Local Health District's Human Research Ethics Committee (HREC 17/092). The results of this trial will be disseminated in peer-reviewed proceedings (associated with conference presentation) and in scholarly journals. TRIAL REGISTRATION NUMBER: ACTRN12619001121156.

Associations of ARMS2 and CFH Gene Polymorphisms with Neovascular Age-Related Macular Degeneration.

PURPOSE: This study aimed to determine the association of ARMS2 A69S, ARMS2 del443ins54, and CFH Y402H polymorphisms with neovascular age-related macular degeneration (nAMD) for the first time in an Indonesian population. PATIENTS AND METHODS: Our case-control study involved 104 nAMD and 100 control subjects. AMD diagnosis was evaluated by retinal specialists based on color fundus photography and optical coherence tomography. The polymorphisms on CFH Y402H and ARMS2 A69S were analyzed by PCR-restriction fragment length polymorphism (PCR-RFLP), whereas ARMS2 del443ins54 was evaluated by PCR-based assay. RESULTS: Significant allelic associations with nAMD were detected on all polymorphisms (P<0.05), with stronger association with the ARMS2 A69S (OR 3.13; 95% CI 2.08-4.71; P<0.001) and ARMS2 del443ins54 (OR 3.28; 95% CI 2.17-4.95; P<0.001) polymorphisms than with CFH Y402H (OR 2.08; 95% CI 1.08-3.99; P=0.028). Genotype analysis showed a statistical difference between nAMD and the control group for all polymorphisms (P<0.05). However, the association with nAMD was weaker for CFH Y402H (P=0.043) than for ARMS2 A69S and ARMS2 del443ins54 (P<0.001). A significant interaction between ARMS2 A69S and hypertension was documented (OR 9.53; 95% CI 3.61-25.1; P<0.001). CONCLUSION: Our findings indicate that ARMS2 A69S and ARMS2 del443ins54 polymorphisms are strongly associated with the risk of nAMD for the first time in an Indonesian population. The risk of nAMD increased when the presence of risk alleles from ARMS2 A69S was combined with the presence of hypertension.

Retinal arteriolar changes: intermediate pathways linking early life exposures to cardiovascular disease?

Low birth weight is an indicator of exposure to unfavorable fetal environment and has been associated with the development of hypertension and cardiovascular disease in adulthood. There is now growing evidence suggesting that alterations in the microcirculation associated with exposure to a suboptimal in utero environment play a key role in the development of cardiovascular disease. Proposed hypothetical mechanisms include: fetal circulatory redistribution, impaired synthesis of elastin, and endothelial dysfunction in response to antenatal and postnatal environment. More recent studies have shown associations of low birth weight with capillary rarefaction and narrowing retinal arteriolar caliber in both children and adults. This suggests that vascular adaptations in utero persist into maladaptive circulatory changes in adulthood, which may reflect an increased susceptibility to hypertension and cardiovascular disease later in life. Therefore, the association between low birth weight and narrower retinal arteriolar caliber, together with associations between narrower retinal arteriolar caliber and risk of hypertension and cardiovascular disease, suggest that retinal arteriolar narrowing may be a marker on the microvascular pathway and mechanisms linking early life exposures and subsequent cardiovascular disease.

The estimated healthcare cost of diabetic retinopathy in Indonesia and its projection for 2025.

PURPOSE: To estimate the total healthcare cost associated with diabetic retinopathy (DR) in type 2 diabetes in Indonesia and its projection for 2025. METHODS: A prevalence-based cost-of-illness model was constructed from previous population-based DR study. Projection for 2025 was derived from estimated diabetes population in 2025. Direct treatment costs of DR were estimated from the perspective of healthcare. Patient perspective costs were obtained from thorough interview including only transportation cost and lost of working days related to treatment. We developed four cost-of-illness models according to DR severity level, DR without necessary treatment, needing laser treatment, laser +intravitreal (IVT) injection and laser + IVT +vitrectomy. All costs were estimated in 2017 US$. RESULTS: The healthcare costs of DR in Indonesia were estimated to be $2.4 billion in 2017 and $8.9 billion in 2025. The total cost in 2017 consisted of the cost for no DR and mild-moderate non-proliferative DR (NPDR) requiring eye screening ($25.9 million), severe NPDR or proliferative DR (PDR) requiring laser treatment ($0.25 billion), severe NPDR or PDR requiring both laser and IVT injection ($1.75 billion) and advance level of PDR requiring vitrectomy ($0.44 billion). CONCLUSIONS: The estimated healthcare cost of DR in Indonesia in 2017 was considerably high, nearly 2% of the 2017 national state budget, and projected to increase significantly to more than threefold in 2025. The highest cost may incur for DR requiring both laser and IVT injection. Therefore, public health intervention to delay or prevent severe DR may substantially reduce the healthcare cost of DR in Indonesia.

Neurofibromatosis type 2 gene mutation and progesterone receptor messenger RNA expression in the pathogenesis of sporadic orbitocranial meningioma.

AIM: To investigate neurofibromatosis type 2 (NF2) gene mutation at mRNA levels in sporadic orbitocranial meningioma and its association with progesterone receptor (PR) mRNA expression. METHODS: This was a case-control study. Thirty-four sporadic meningioma patients with no familial NF2-related meningioma history were recruited. They were interviewed for their obstetric, gynecologic, and contraception history. PR investigation was performed with real-time polymerase chain reaction (PCR). NF2 mutation was investigated using Qbiomarker Somatic Mutation PCR Assay at NF2 mRNA level after its cDNA extraction (four mRNA mutation cytoband coordinates for nucleotide change: c.634C>T/p.Q212, c.655G>A/p.V219M, c.784C>T/p.R262 and c.1228C>T/p. Q410). RESULTS: After mutation analysis at mRNA level, NF2 gene mutation was found in 35.29% patients. Non-mutation group was strongly associated with exogenous hormonal exposure (non-mutation vs mutation: 95.5% vs 83.3%, P<0.001). PR mRNA was found significantly lower in non-mutation group (P=0.033) which presumed as long term exogenous progesterone exposure. However, mutation group was associated with higher rate of progression to grade II (mutation vs non-mutation, 18.2% vs 5%, P<0.001) and was associated more in fibrous and anaplastic tumor tissue. CONCLUSION: NF2 mutation-meningioma is associated with higher grade of meningioma. Non NF2 mutation-meningioma is strongly associated with exogenous progesterone exposure and lower PR expression.