High hydroxyurea usage in sickle cell anemia regardless of patient demographics.

Hydroxyurea is highly effective in sickle cell disease, but it is still underutilized. Reports of hydroxyurea utilization largely use Medicaid data, and socioeconomics is often cited as a barrier. To address whether patient demographics influenced the high hydroxyurea usage rate recently reported for the pediatric sickle cell program of Northern Virginia, analysis of data from 2011 to 2021 revealed no statistical difference in hydroxyurea usage rate between Medicaid and non-Medicaid, African American and African, or age less than 13 and age greater than or equal to 13 years cohorts, demonstrating that hydroxyurea can be successfully implemented across demographic groups.

CLINICAL FEATURES AND SURGICAL OUTCOMES OF SCLERAL BUCKLE SURGERY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: Moorfields Buckle Study.

PURPOSE: Long-term study to evaluate the clinical and surgical outcomes of scleral buckle (SB) surgery for primary rhegmatogenous retinal detachment (RRD) at a large tertiary eye center. METHODS: Noncomparative, retrospective case series of 589 eyes of 569 patients with primary RRD who underwent SB surgery between 2004 and 2022 with a median follow-up of 6 months. The main outcome measures were best-corrected visual acuity, surgical outcomes, complications, and classification of RRD. RESULTS: At baseline, 447/589 (76.1%) round hole RRD, and 133/589 (22.7%) retinal dialysis RRD. Overall primary SB success rate was 83.7% for all retinal detachment subtypes, with round hole retinal detachment 84.8% and dialysis RRD 81.2%. Overall, the baseline best-corrected visual acuity was 0.42 logarithm of the minimum angle of resolution (logMAR) and the final best-corrected visual acuity was 0.26 logMAR ( P < 0.0001). In macula-off RRD, the best-corrected visual acuity significantly improved from 0.79 to 0.48 logMAR ( P < 0.0001). In patients with macula-on RRD, it improved from 0.19 to 0.12 logMAR ( P = 0.014). Binary logistic regression showed registrar surgeon grade (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01-0.55), and partial or complete posterior vitreous detachment (OR 0.21, 95% CI 0.10-0.49) was associated with reduced odds of primary success. Higher surgical failure was associated with low pre-fellowship SB surgeon experience ( P = 0.024). CONCLUSION: Favorable visual and functional outcomes have been reported in a large series of SB for primary retinal detachment, mainly for patients with round hole RRD and retinal dialysis RRD.

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study.

BACKGROUND: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. METHODS: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. RESULTS: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. CONCLUSION: In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.

A randomised controlled provider-blinded trial of community health workers in sickle cell anaemia: effects on haematologic variables and hydroxyurea adherence.

Hydroxyurea (hydroxycarbamide) (HU) for sickle cell anaemia (SCA) is underutilised. Case management is an evidence-based health management strategy and in this regard patient navigators (PNs) may provide case management for SCA. We hypothesised that HU-eligible patients exposed to PNs would have improved indicators of starting HU and HU adherence. We randomised 224 HU-eligible SCA adults into the Start Healing in Patients with Hydroxyurea (SHIP-HU) Trial. All patients received care from trained physicians using standardised HU prescribing protocols. Patients in the Experimental arm received case management and education from PNs through multiple contacts. All other patients were regarded as the Control arm and received specialty care alone. Study physicians were blinded to the study arms and did not interact with PNs. At baseline, 6 and 12 months we assessed and compared laboratory parameters and HU adherence indicators. Experimental patients had higher 6-month mean fetal haemoglobin (HbF) levels than controls. But at 12 months, mean HbF was similar, as were white blood cell count, absolute neutrophil count, total haemoglobin, platelet count and mean corpuscular volume. At 12 months there were fewer experimental patients missing HU doses than controls (mean 1·8 vs. 4·5, P = 0·0098), and more recent HU prescriptions filled than for controls (mean 53·8 vs. 92 days, median 27·5 vs. 62 days, P = 0·0082). Mean HU doses were largely similar. We detected behavioural improvements in HU adherence but no haematological improvements by adding PNs to specialty care.

Ten-year longitudinal analysis of hydroxyurea implementation in a pediatric sickle cell program.

Hydroxyurea (HU) has proven benefit in sickle cell anemia (SCA), but HU is still underutilized. The Pediatric Sickle Cell Program of Northern Virginia prescribes HU regardless of symptoms to all SCA patients age ≥ 9 months and prospectively tracks outcomes. HU is dosed to maximum tolerated dosing (MTD), targeting 30% Hgb F. Longitudinal data from 2009 to 2019 encompassing 1222 HU-eligible and 950 HU-exposure patient-years were analyzed in 2-year intervals for hemoglobin (Hgb), fetal hemoglobin (Hgb F), hospitalizations, transfusions, and treat-and-release ED visits. Comparing HU-eligible patients in the interval prior to HU implementation (2009-2011) to the last interval analyzed after HU implementation (2017-2019), HU usage increased from 33% to 93%, average Hgb increased from 8.3 ± 0.98 to 9.8 ± 1.3 g/dl (p < .0001), average Hgb F rose from 13 ± 8.7% to 26 ± 9.9% (p < .0001), hospitalizations decreased from 0.71 (95% CI 0.54-0.91) to 0.2 (95% CI 0.13-0.28) admissions/person-year, sporadic transfusions decreased from 0.4 (95% CI 0.27-0.55) to 0.05 (95% CI 0.02-0.12) transfusions/person-year. Treat-and-release ED visit rates remained unchanged, varying between 0.49 (95% CI 0.36-0.64) and 0.64 (95% CI 0.48-0.83) visits/person-year. By the last interval, 72% of patients had Hgb ≥ 9 g/dl, 42% had Hgb F ≥ 30%, 79% experienced no hospitalizations, and 94% received no transfusions. Uniform HU prescription for SCA patients with close monitoring to achieve high Hgb F resulted in significant improvements in laboratory and clinical outcomes within 2 years, which continued to improve over the next 6 years. Rigorous HU implementation in a pediatric sickle cell population is feasible, effective, and sustainable.

Gut microbial composition difference between pediatric ALL survivors and siblings.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with high cure rates leading to rising numbers of long-term survivors. Adult survivors of childhood ALL are at increased risk of obesity, cardiovascular disease, and other chronic illnesses. We hypothesize that ALL therapy is associated with long-term gut microbiome alterations that contribute to predisposition to chronic medical conditions. We conducted a pilot study to test whether differences can be detected between stool microbiota of pediatric ALL survivors and their siblings. Stool samples were collected from 38 individuals under age 19 who were at least 1 year after completion of therapy for ALL. Stool samples collected from 16 healthy siblings served as controls. 16S ribosomal RNA gene sequencing was performed on the stool samples. Comparing microbiota of survivors to sibling controls, no statistically significant differences were found in alpha or beta diversity. However, among the top 10 operational taxonomic units (OTUs) from component 1 in sparse partial least squares discriminant analysis (sPLS-DA) with different relative abundance in survivors versus siblings, OTUs mapping to the genus Faecalibacterium were depleted in survivors. Differences in gut microbial composition were found between pediatric survivors of childhood ALL and their siblings. Specifically, the protective Faecalibacterium is depleted in survivors, which is reminiscent of gut microbiota alteration found in adult survivors of childhood ALL and reported in obesity, suggesting that microbiota alterations in pediatric ALL survivors start in childhood and may play a role in predisposition to chronic illness in later years of survivorship.

Genome sequencing analysis of blood cells identifies germline haplotypes strongly associated with drug resistance in osteosarcoma patients.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children. Survival remains poor among histologically poor responders, and there is a need to identify them at diagnosis to avoid delivering ineffective therapy. Genetic variation contributes to a wide range of response and toxicity related to chemotherapy. The aim of this study is to use sequencing of blood cells to identify germline haplotypes strongly associated with drug resistance in osteosarcoma patients. METHODS: We used sequencing data from two patient datasets, from Inova Hospital and the NCI TARGET. We explored the effect of mutation hotspots, in the form of haplotypes, associated with relapse outcome. We then mapped the single nucleotide polymorphisms (SNPs) in these haplotypes to genes and pathways. We also performed a targeted analysis of mutations in Drug Metabolizing Enzymes and Transporter (DMET) genes associated with tumor necrosis and survival. RESULTS: We found intronic and intergenic hotspot regions from 26 genes common to both the TARGET and INOVA datasets significantly associated with relapse outcome. Among significant results were mutations in genes belonging to AKR enzyme family, cell-cell adhesion biological process and the PI3K pathways; as well as variants in SLC22 family associated with both tumor necrosis and overall survival. The SNPs from our results were confirmed using Sanger sequencing. Our results included known as well as novel SNPs and haplotypes in genes associated with drug resistance. CONCLUSION: We show that combining next generation sequencing data from multiple datasets and defined clinical data can better identify relevant pathway associations and clinically actionable variants, as well as provide insights into drug response mechanisms.

Prospective longitudinal follow-up of children with sickle cell disease treated with hydroxyurea since infancy.

BACKGROUND: Hydroxyurea (HU) increases fetal hemoglobin (HgbF) and ameliorates sickle cell disease (SCD) symptoms. Studies have demonstrated the safety and efficacy of HU in infants and children. Initiation of HU in infancy for children with SCD needs to be implemented in community practice. PROCEDURE: Starting in 2011, the Pediatric Sickle Cell Program of Northern Virginia initiated HU in infants with SCD. A prospective longitudinal database tracked the clinical course and outcomes. RESULTS: Twenty-four children with HgbSS who started HU by age 1 were continuously followed for a total of 95 person-years. Age at the time of analysis ranged from 2 to 7 years. Average hemoglobin at 6-month intervals ranged from 9.5 + 1.9 to 10.7 + 0.8 g/dL, and average HgbF ranged from 27.8 + 5.0% to 34.1 + 6.6%. Twenty-seven hospitalizations occurred (0.28/person-year), all before age 3, including 19 (70%) for fever or infection, five (19%) for splenic sequestration, and one (4%) for pain in an infant prior to starting HU. The treat-and-release emergency department visits totaled 68 (0.72/person-year), including 62 visits (91%) for fever, infection, or viral illness, and two visits (3%) for pain/dactylitis in infants before HU initiation. Splenic sequestration accounted for all five transfusions. No pain episodes requiring medical attention were documented after HU initiation. No complicated acute chest syndrome, no abnormal or conditional transcranial Doppler ultrasound, and no overt strokes occurred. CONCLUSION: Implementation of HU in infancy for patients with SCD in community practice is feasible and is highly effective in preventing disease complications.

Molecular characterization and multidisciplinary management of Gerbich hemolytic disease of the newborn.

Gerbich (Ge) antigens are high frequency red cell antigens expressed on glycophorin C (GYPC) and glycophorin D. Hemolytic disease of the fetus and newborn (HDFN) due to Gerbich antibody is rare and presents a clinical challenge, as Gerbich negative blood is scarce. We report a case of HDFN due to maternal Ge3 negative phenotype and anti-Ge3 alloimmunization, successfully managed by transfusion of maternal blood. Molecular testing revealed that the mother has homozygous deletion of exon 3 of GYPC, the father is homozygous wildtype for GYPC, and the infant is obligate heterozygote expressing Ge3.

Distinctive barriers to antiretroviral therapy adherence among non-adherent adolescents living with HIV in Botswana.

Levels of adherence to HIV treatment are lower among adolescents compared with older and younger individuals receiving similar therapies. We purposely sampled the most and least adherent adolescents from a 300-adolescent longitudinal HIV treatment adherence study in Gaborone, Botswana. Multiple objective and subjective measures of adherence were available and study participants were selected based on sustained patterns of either excellent or poor adherence over a one-year period. Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with the adolescents and a subset of their caregivers with the goal of revealing barriers and facilitators of adherence. Focus groups were segregated by adherence classification of the participants. Following coding of transcripts, matrices were developed based on participants' adherence classifications in order to clarify differences in themes generated by individuals with different adherence characteristics. 47 adolescents and 25 adults were included. The non-adherent adolescents were older than the adherent adolescents (median age 18 years (IQR 16-19) vs. 14 years (IQR 12-15 years)), with median time on treatment near 10 years in both groups. Interference with daily activities, concerns about stigma and discrimination, side effects, denial of HIV status, and food insecurity arose as challenges to adherence among both those who were consistently adherent and those who were poorly-adherent to their medications. Low outcome expectancy, treatment fatigue, mental health and substance use problems, and mismatches between desired and received social support were discussed only among poorly adherent adolescents and their caregivers. Challenges raised only among adolescents and caregivers in the non-adherent groups are hypothesis-generating, identifying areas that may have a greater contribution to poor outcomes than challenges faced by both adherent and non-adherent adolescents. The contribution of these factors to poor outcomes should be explored in future studies.

Surgical management of raised intra-ocular tension in the hostile ocular surface - recurrent tube erosion in a patient with systemic sclerosis: a case report.

BACKGROUND: The surgical management of patients with uncontrolled glaucoma and scleroderma is challenging, as the hostile ocular surface poses a challenge to surgery. A serious complication is tube erosion, with the risk of subsequent endophthalmitis. Here, we present a novel technique of harvesting autologous tissue to successfully manage recurrent tube extrusion. CASE PRESENTATION: MG is a 60-year-old Arabic lady diagnosed with scleroderma, that was previously managed with systemic corticosteroids. She has chronic open angle glaucoma, with a failed left eye trabeculectomy, which was then managed by a Baerveldt tube (BVT) insertion. Eight months after this primary surgery, she developed an anterior uveitis. This was further complicated by conjunctival erosion, tube exposure, leak around the sclerostomy site and hypotony. The erosion was likely secondary to her tight eyelids as a result of her scleroderma. She was taken back to theatre for tube revision, with single layer amniotic membrane transplant (AMT) over the exposed area, but the tube was eroding again after 2 months. She eventually underwent tube extraction, pars plana tube plate stabilisation, pars plana vitrectomy (PPV), pars plana tube insertion, phacoemulsification and intra-ocular lens insertion, jointly with the vitreo-retinal surgeons and with high dose prednisolone cover both pre- and post-operatively. We harvested the capsule which had grown over the end plate of the original tube. We sutured this over the new tube, specifically over a single layer of tutoplast prior to conjunctival closure. Almost a year on, the pars plana tube remains in place with no complications. CONCLUSIONS: This case highlights the role of a pars plana tube in cases of cicatricial disease, with the use autologous tissue instead of grafts wherever possible. In patients with systemic disease such as scleroderma, pre-operative immunosuppression helps to reduce the of erosion in difficult cases.

Hemoglobin C trait accentuates erythrocyte dehydration in hereditary xerocytosis.

A 17-year-old male presented with acute hemolysis with stomatocytosis, elevated mean corpuscular hemoglobin concentration (MCHC), and osmotic gradient ektacytometry consistent with marked erythrocyte dehydration. Erythrocytes from both parents also demonstrated evidence of dehydration with elevated MCHC and abnormal ektacytometry, but neither to the degree of the patient. Genetic studies revealed the patient had hereditary xerocytosis (HX) due to a novel PIEZO1 mutation inherited from his mother and hemoglobin C (HbC) trait inherited from his father. HbC trait accentuated the erythrocyte dehydration of HX. Coinheritance of interrelated disorders and/or modifier alleles should be considered whenever severe erythrocyte dehydration is observed.

Discontinuation of Folic Acid Supplementation in Young Patients With Sickle Cell Anemia.

Folic acid (FA) is commonly prescribed for patients with sickle cell anemia, but evidence for the efficacy of this practice is lacking. We stopped FA supplementation and measured red blood cell folate levels after discontinuation of FA in 72 patients with clinically severe forms of sickle cell disease. We compared hemoglobin and reticulocyte counts before and after FA discontinuation in 51 of those patients, the majority of whom were on hydroxyurea. No patients had red blood cell folate levels below normal and no significant difference in hemoglobin levels (P=0.18) or reticulocyte counts (P=0.37) was found before and after FA discontinuation.

The natural history of polypoidal choroidal vasculopathy: a multi-center series of untreated Asian patients.

PURPOSE: We aimed to evaluate the long-term natural history of polypoidal choroidal vasculopathy (PCV) in untreated patients. METHODS: This is a retrospective observational case series. Patients with symptomatic PCV who did not receive any treatment for at least 12 months were included from the records of three ophthalmic clinics in Asia. The medical records and imaging data were reviewed. Visual outcomes at month 12 and at last follow-up were analyzed. The influence of demographics and presenting features on visual outcome was analyzed. RESULTS: A total of 32 eyes (32 patients) were included in this analysis. The mean follow-up was 59.9 months (range, 18-119 months), the mean age was 65.7 years and 21 (65.6 %) patients were male. The mean presenting logMAR visual acuity was 0.79 (Standard deviation [SD] 0.49). The center of the fovea was involved by the PCV complex in 25 eyes (78.1 %). The mean greatest linear dimension (GLD) of the PCV complex was 2584 µm (SD 880). Twenty-three eyes (71.9 %) had a cluster-of-grapes configuration on indocyanine green angiography. Leakage of fluorescein angiography was present in 29 eyes (90.6 %). The mean logMAR vision deteriorated from 0.79 at baseline to 0.88 at month 12 (p = 0.11), and further to 1.14 (p = 0.003) at the last follow-up. The proportion of eyes that improved, remained unchanged and worsened was 21.9 %, 31.3 % and 46.9 %, respectively, at month 12; and 28.1 %, 9.4 % and 62.5 %, respectively, at last follow-up. The proportion of eyes with logMAR vision worse than 1.0 was 28.1 % at presentation, and increased to 31.3 % at month 12 and further to 53.1 % at last follow-up. Reasons for poor vision were due to retinal, subretinal or vitreous hemorrhage, and retinal pigment epithelium (RPE) atrophy and scarring. None of the presenting features were found to significantly influence visual outcome. CONCLUSIONS: Half of eyes presenting with symptomatic PCV had a relatively benign course without treatment and some even had vision improvement. However, in the remaining eyes, vision deteriorated significantly, mainly due to hemorrhage and scarring. There may be subtypes of PCV with divergent natural history.

Bilateral dacryocystoceles in a pregnant woman.

The authors describe, for the first time, bilateral, sequential large dacryocystoceles during pregnancy and review the literature for this presentation. A 26-year-old, 15-week pregnant woman presented with OD epiphora, diplopia, and pain in the setting of an inferomedial orbital mass. Surgical exploration and histopathology were consistent with a dacryocystocele, and a dacryocystorhinostomy was curative. She returned at 34-week gestation, with an identical presentation on the left side. Review of the literature reveals that dacryocystoceles occasionally present in adults; however, bilateral involvement may be unusual. Bilateral dacryocystoceles have not been previously reported in a pregnant woman.

Scleral sutured aniridia intraocular lens (Morcher®): indications and long-term outcomes.

BACKGROUND/OBJECTIVE: To evaluate the outcomes of trans-scleral sutured posterior chamber black diaphragm intraocular lens (BDIOL) (Morcher®) implantations over 11 years. SUBJECTS/METHODS: Retrospective case-series of patients, who underwent BDIOL implantation, identified from electronic patient records system from 2006 to 2016, Moorfields Eye Hospital. Demographics, pre/post-operative, final best-corrected visual acuity (BCVA), diagnosis, symptomatic improvement, intraoperative and postoperative complications immediate or late were collected and analysed to relate outcomes to surgical indication. RESULTS: Forty eyes of 38 patients (F:M 1:2.8) underwent BDIOL implantation with a mean surgical age of 46.6 years and follow-up of 44.5 months (range of 8-132 months). Indications included 23(57%) ocular trauma, 7(17%) congenital aniridia, 7(17%) iatrogenic lens and/or iris loss, and 3(7%) infectious keratitis. Mean preoperative BCVA was 1.64 logMAR and mean final postoperative BCVA was 0.94 logMAR with an average improvement in BCVA of 0.23 logMAR, equivalent to 1.5 lines of Snellen visual acuity. Visual results varied according to indications. Infectious cause patients had the greatest vision improvement (-0.7 logMAR), followed by trauma (-0.3 logMAR), and 25% of these achieved vision of 0.3 logMAR (6/12 in Snellen acuity) or better. Conversely, the aniridia group had the least improvement (worsened vision of 0.01 logMAR), 17 patients (42%) reported subjective improvement. CONCLUSION: BDIOLs achieve reasonably good visual outcomes in eyes with complex vision threatening pathology. No significant intra-operative complications are documented and most post-operative complications are related to the pre-existing pathology. Post - trauma and iatrogenic aniridia have better outcomes compared to congenital aniridia.

Hypomorphic mutations of SEC23B gene account for mild phenotypes of congenital dyserythropoietic anemia type II.

Congenital dyserythropoietic anemia type II, a recessive disorder of erythroid differentiation, is due to mutations in SEC23B, a component of the core trafficking machinery COPII. In no case homozygosity or compound heterozygosity for nonsense mutation(s) was found. This study represents the first description of molecular mechanisms underlying SEC23B hypomorphic genotypes by the analysis of five novel mutations. Our findings suggest that reduction of SEC23B gene expression is not associated with CDA II severe clinical presentation; conversely, the combination of a hypomorphic allele with one functionally altered results in more severe phenotypes. We propose a mechanism of compensation SEC23A-mediated which justifies these observations.

Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170). METHODS: Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. RESULTS: The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background. CONCLUSIONS: There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD.