Investigating the CFH Gene Polymorphisms as a Risk Factor for Age-related Macular Degeneration in an Iranian Population

Background: Age-related macular degeneration (AMD) is a complex disorder which results in irreversible vision loss and progressive impairment of central vision. Disease susceptibility is influenced by multiple genetic and environmental factors. Single nucleotide polymorphisms (SNP) in the complement factor H gene are the most important genetic risk factors. We conducted a case-control study to investigate the association four SNPs (dbSNP ID: rs800292, rs1061170, rs2274700 and rs3753395) of CFH gene with AMD in the Iranian population.

Materials and Methods: We recruited 100 AMD patients and 100 age- and sex-matched normal controls. Direct sequencing for three SNPs (rs800292, rs2274700 and rs3753395) and restriction fragment length polymorphism utilized for rs1061170. Allele and genotype frequencies of SNPs were calculated and tested for departure from Hardy–Weinberg equilibrium using the Chi-square test. An allelic and genotypic association was compared by logistic regression analysis using the SNPassoc.

Results: According to our results, the frequencies of risk allele for all SNPs (G, G, A, and C alleles of rs800292, rs2274700, rs3753395 and rs1061170, respectively) were significantly higher in AMD patients (p value < 0.001). AMD individuals who had at least one copy of the C allele of rs1061170 had an increased risk of disease compared with cases with the T allele. Other studied polymorphisms showed the same association.

Conclusion: Our results suggest the contribution of all four predicted CFH polymorphisms in AMD susceptibility among the Iranian population. This association with CFH may lead to early detection and new strategies for prevention and treatment of AMD.     

ENOS polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Chinese Han population

Purpose: To investigate whether common genetic variants in the endothelial nitric oxide synthase gene (eNOS) are associated with neovascular age-related macular degeneration (nAMD) and polypoidal choroidalvasculopathy (PCV) in a Chinese Han population.

Methods: DNA samples were obtained from 157 nAMD patients, 250 PCV patients and 204 healthy control subjects. Tag single nucleotide polymorphisms (SNPs) across the extended eNOS region were selected using data derived from the HapMap project. Genotyping of each tag SNP was performed by Multiplex SNaPshot system and direct DNA sequencing techniques. Genotypes and allele frequencies were evaluated with PLINK software for each group.

Results: Seven SNPs for eNOS, rs1799983, rs1800783, rs3918186, rs3800787, rs3918188, rs7830, and rs3918227, were chosen as tag SNPs. Among these tag SNPs, rs1800783, rs3918186, rs3918188, and rs3918227 were not associated with nAMD or PCV. Rs1799983, rs3800787, and rs7830 was significantly associated with nAMD (p = 0.0192, 0.0170, and 0.0164, respectively), but not associated with PCV (p = 0.4852, 0.4568, and 0.4014, respectively). The discovered associations were no longer significant after Bonferroni correction.

Conclusions: We found no sufficient evidence to support the role of any common eNOS variants in the susceptibility to nAMD or PCV in a Chinese Han population.     

Leuconostoc as a Cause of Endophthalmitis Post-intravitreal Injection of Ranibizumab

Purpose: The authors report a case of endophthalmitis after intravitreal injection of ranibizumab.

Methods: After searching for extensive laboratory tests to isolate the etiologic agent

Results: The agent was determined as Leuconostoc mesenteroides, gram-positive cocci, vancomycin resistant.

Discussion: Considerations regarding this bacterium were done by calling attention to its rarity, difficulty of isolation, and action on secondary comorbidities as opportunistic pathogen.     

Stroke Due to Cerebral Vasculitis in a Patient with Relentless Placoid Chorioretinitis

Purpose: To report the first case of stroke in a patient with relentless placoid chorioretinitis.

Methods: Observational case report.

Results: A 20-year-old female with newly diagnosed relentless placoid chorioretinitis was urgently evaluated for unilateral paresthesias. She was found to have acute bilateral pontine strokes and cerebral vasculitis on magnetic resonance imaging of the brain and cerebral angiography.

Conclusions: We report the first case of stroke due to cerebral vasculitis in a patient with relentless placoid chorioretinitis. This case emphasizes the need for timely evaluation of neurological symptoms in patients with this ocular diagnosis.     

Pharmacogenetic Aspect of Intravitreal Ranibizumab Treatment in Neovascular Age-Related Macular Degeneration: A Five-Year Follow-Up

Purpose: This study aims to evaluate the role of complement factor H (CFH) in response to intravitreal ranibizumab (IVR) treatment, which is administered to patients with neovascular age-related macular degeneration (nAMD).

Methods: In this retrospective study, 90 nAMD patients’ 90 eyes were evaluated. IVR was injected once a month for three consecutive months, and then, patients were followed up for five years by using pro re nata method.

Results: Average visual acuity (BCVA) values in TT group for the third, fourth and fifth years were found to be significantly higher than those in TC and CC groups, while average BCVA values in TC group were significantly higher than those in CC group (all p = .000 < .0167).

Conclusion: Patients with CFH TT genotype responded significantly better to treatment after third year, while patients with CC genotype had a poorer response to IVR.     

Evaluation of Aqueous Flare Levels Following Intravitreal Ranibizumab Injection for Neovascular Age-related Macular Degeneration

Purpose: To evaluate aqueous flare levels following intravitreal ranibizumab injection for neovascular age-related macular degeneration (AMD).

Methods: In total, 81 eyes of 79 patients who underwent intravitreal ranibizumab injection for neovascular AMD were included. Aqueous flare was evaluated before pupillary dilatation with Kowa FM-600 laser flare meter at baseline, and 1 day, and 1 month after intravitreal administration of ranibizumab 0.5 mg (0.05 mL).

Results: The mean anterior chamber flare was 10.7 ± 6.8 (range: 1.5–35.4) ph/ms before the injection, 12.5 ± 8.9 (range: 0.3–43) ph/ms on the first day, and 9.9 ± 5.7 (range: 0.2–28.4) ph/ms in the first month. On the first day, a subtle increasing of flare was observed. However, the difference between the mean aqueous flare levels at baseline and postoperative first day and first month was not statistically different (p>0.05).

Conclusions: No significant short-term intraocular inflammation was noted in these eyes receiving ranibizumab for the treatment of neovascular AMD.     

Predicting Non-response to Ranibizumab in Patients with Neovascular Age-related Macular Degeneration

Purpose: To validate known and determine new predictors of non-response to ranibizumab in patients with neovascular age-related macular degeneration (AMD) and to incorporate these factors into a prediction rule.

Methods: This multicenter, observational cohort study included 391 patients treated with ranibizumab for neovascular AMD. We performed genetic analysis for single nucleotide polymorphisms in AMD-associated genes and collected questionnaires regarding environmental factors and disease history. The primary outcome was non-response to treatment, defined as a loss of visual acuity ≥30% of letters.

Results: Of the 391 patients, 47 were classified as non-responsive. Independent predictors for non-response were age, baseline visual acuity, diabetes mellitus and accumulation of risk alleles in the CFH, ARMS2 and VEGF-A genes. The area under the receiver operating characteristic curve was 0.77 (95% confidence interval 0.70–0.84). We derived a clinical prediction rule, with possible total risk scores ranging from 0–19 points. The absolute risk of non-response varied from 3–52% between risk score groups.

Conclusion: This is an important step towards a clinical prediction rule that can aid clinicians in identifying AMD patients with increased likelihood of non-response, and consequently contribute to making shared treatment decisions.     

Intraocular Lymphoma Masquerading as Recurrent Iridocyclitis: Findings Based on in vivo Confocal Microscopy

Purpose: To emphasize the application prospects of in vivo confocal microscopy (IVCM) in distinguishing intraocular lesions from inflammatory and neoplastic diseases.

Methods: Retrospective case report.

Results: A patient with neoplastic masquerade syndrome initially underwent IVCM examination. After six separate intravitreal injections of 400 mg/0.1 ml methotrexate, IVCM revealed a complete remission of intraocular lymphoma.

Conclusions: Although IVCM findings alone are not enough to diagnose intraocular neoplasm with absolute certainty, they can provide useful indication for distinguishing between intraocular inflammatory diseases and neoplasms.     

Photoreceptor Cell Injury Starts in the Initial Stage of Vogt–Koyanagi–Harada Disease

Purpose: To demonstrate photoreceptor cell injury in Vogt-Koyanagi-Harada (VKH) disease.

Methods: The SD-OCT and FAF tests of 16 patients diagnosed with VKH disease that was followed up from the initial stage to the convalescent stage were reviewed.

Results: In the initial stage of VKH disease, there was hyperautofluerescence around the macular edema. In the convalescent stage of VKH disease, loss of photoreceptor and injury of RPE have been detected by OCT scan at the same area, which was corresponded with the abnormalities in FAF.

Conclusions: The VKH disease causes photoreceptor injury starting in the initial stage of the disease.     

Analysis of Clinical Profile,Investigation, and Management of Ocular Cysticercosis Seen at a Tertiary Referral Centre

Aim: To analyze the demographic profile, clinical presentation, diagnosis, management, and outcome of ocular cysticercosis (OC) seen at a tertiary referral center.

Design: Retrospective case series.

Material and methods: Records of patients with diagnosis of OC from January 2000 to September 2015 were retrieved and the data was analyzed.

Results: 102 eyes of OC were seen. 72(71%) eyes had extraocular cysticercosis (EC) and 30(29%) eyes had intraocular cysticercosis (IC). EC was located in the orbit in 69/72 (96%) eyes. Symptoms of extraocular cysticercosis were restriction of ocular movement in 33 eyes (46%). IC was located in vitreous 17 eyes (57%). Symptom of IC was drop in vision in 26/30 eyes (87%). EC was managed medically with albendazole and steroid. Surgical excision was done for IC.

Conclusion: EC was more common than IC. Prompt and appropriate management of OC results in good visual outcome.     

Impact of Superior Oblique Transposition on Primary Position Deviation,a Pattern and Intorsion in Third Nerve Palsy

Purpose: To evaluate the role of superior oblique transposition on primary position alignment, A pattern, and intorsion in third nerve palsy.

Methods: Ten patients with isolated, unilateral third nerve palsy were included in this prospective study. The patients were treated by conventional surgery on horizontal recti together with superior oblique transposition by Scott’s procedure in the paretic eye.

Results: Pre-operative primary horizontal deviation was 60-80 PD (mean 70.00±7.45 PD). Pre-operative primary hypotropia was 15-22 PD (mean 18.80±2.48 PD). Mean A-pattern was 17.80±2.65 PD. All patients included in the study had some degree of objective torsion as measured by Guyton’s method. One patient had grade I objective intorsion, 2 had grade II, 6 had grade III, and 1 had grade IV objective intorsion.

Primary position horizontal alignment (up to ±8 PD) was achieved in 9 patients. Primary position vertical alignment (up to ±8 PD) was achieved in all 10 patients.

Only 2 of 10 patients had A-pattern of 10 PD, in the remaining 8 patients it was eliminated (P<0.05). Postoperatively, 5 patients had no objective intorsion and 5 had grade I intorsion, and none of the patients had hypertropia or paradoxical eye movements.

Conclusion: Superior oblique transposition by Scott’s procedure along with conventional surgery on horizontal recti in third nerve palsy results in better horizontal and vertical alignment, and improves A-pattern and intorsion, thus leading to better binocular interaction.     

Joint association of complement component 3 and CC-cytokine ligand2 (CCL2) or complement component 3 and CFH polymorphisms in age-related macular degeneration

Background: To determine the joint effect of complement component 3(C3 R102G) with CC-cytokine ligand2 (CCL2-2518) or complement factor H (CFH) Y402H polymorphisms on advanced age-related macular degeneration (AMD).

Methods: In this case-control study, 233 patients with advanced AMD and 159 unrelated healthy controls enrolled for evaluation. Selected polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism.

Results: A combination of AA CCL2 (rs1024611) and GG C3 (R102G) genotypes resulted in a super-additivity of the risks: OR = 10.13, 95% CI 1.04–98.49, p = 0.04, adjusted OR = 7.74, 95% CI 0.71–84.75, p < 0.1, adjusted synergy indices: relative excess risk due to interaction (RERI) = 1.38, the attributable proportion due to interaction (AP) = 24.7% and the synergy index (S) = 1.43. Combination of at-risk genotypes of CFH Y402H and C3 R102G resulted in a strong super-additive risk: adjusted OR = 22.65, 95% CI 2.32–220.91, p = 0.007, adjusted AP = 90.4% and the S = 12.86. Attributable proportion of risk owing to C3-CCL2 and C3-CFH interaction calculated at 25% and 90% for advanced AMD.

Conclusion: We have previously shown a strong association of C3 (R102G) and CFH Y402H with AMD whereas no association was found for CCL2-2518. This study enclosed strong synergistic association of risk genotypes of C3 and CFH Y402H with AMD. We also revealed synergistic influence of CCL2-2518 and the at-risk genotype of the C3 in AMD with an estimated AP = 50.9% (adjusted AP = 24.7%). Present findings show that CCL2-2518 polymorphism is not an innocent bystander in AMD susceptibility when combined with the at-risk genotype of C3 (R102G).     

Salmonella Typhi Associated Endogenous Endophthalmitis: A Case Report and a Review of Literature

Aim: To report a rare case of Salmonella typhi associated endogenous endophthalmitis in an immunocompetent male and to review the available literature.

Methods: Retrospective chart review.

Results: A 28-year-old immunocompetent male presented with a 3-day-old history of pain, redness and diminished vision in his left eye. Conjunctival chemosis, corneal haze, and hypopyon were noted and yellowish exudates filled the vitreous cavity. A detailed elicitation of history revealed that patient had been treated for enteric fever that presented with diarrhea and fever, two weeks prior to current presentation. Blood and vitreous cultures grew Gram negative bacilli, identified as S. typhi. Despite intensive intravitreal and systemic antibiotic therapy, an evisceration had to be performed.

Conclusions: Endogenous endophthalmitis can be one of the rare sequelae of enteric fever and may present in the acute and relapsing phases and often times have a rapidly fulminant course with poor visual outcomes.     

Roth Spots in Ocular Toxoplasmosis

Purpose: To report a case with unilateral preexisting ocular toxoplasmosis (OT) and newly occurred active retinochoroidal inflammation associated with white-centered retinal hemorrhages (Roth spots) in the healthy eye.

Design: Case report.

Methods: A 20 year-old man presented with a decrease of visual acuity in his right eye associated with 2+ cells in the anterior chamber. Ophthalmoscopy revealed an active retinochoroidal lesion on the upper nasal border of the optic disc associated with local hemorrhage and vitritis. The posterior pole presented white-centered flame-shaped retinal hemorrhages.

Results: Toxoplasmosis serology showed an IgG titer >300IU/ml and a negative IgM titer. A complete blood count revealed no abnormalities; other serologies were negative. After 2 weeks of treatment with sulfadiazine, pyrimethamine, folinic acid and prednisone, although the peripapillary lesion was still active, the Roth spots disappeared.

Conclusion: OT may be one differential diagnosis of patients suffering Roth spots in association with retinochoroidal inflammation.     

The Effect of Closed-Eye Tear Film Conditions on Blood-Isolated Neutrophils,In Vitro

Purpose: Eyelid closure results in influx of neutrophils onto the ocular surface, which are non-responsive to inflammatory stimuli. This investigation examined whether incubation of blood-isolated neutrophils in closed-eye conditions induce a tear-film neutrophil phenotype.

Methods: Blood-isolated neutrophils were incubated combining various conditions: hypoxia, corneal epithelial cells (HCEC), artificial tear solution (ATS).

Results: A hypoxic environment induced no differential effect on membrane receptor expression. Incubation in the presence of HCEC resulted in membrane receptor upregulation and increase in caspase activation.

Conclusions: Hypoxia, corneal epithelial cell exposure, or artificial tear fluid are insufficient to replicate a tear-film neutrophil phenotype using blood-isolated neutrophils.     

Atypical VZV Retinitis in a Patient with Good Syndrome

Purpose: To describe atypical varicella zoster virus (VZV) retinitis in a patient with Good syndrome.

Methods: A 63-year-old patient with Good syndrome presented with bilateral necrotizing retinitis starting from the posterior pole. He had a history of thymoma status post thymectomy 4 years previously, left-sided sinusitis, and recent pulmonary aspergillosis. Qualitative PCR was performed on aqueous fluid.

Results: Immunological investigations revealed reduced levels of CD4⁺ T cells and immunoglobulins. Qualitative PCR was positive for VZV and negative for cytomegalovirus, herpes simplex virus (HSV)-1, and HSV-2. The patient was treated with oral valacyclovir and three courses of immunoglobulin supplementation. The atypical retinitis showed improvement after therapy.

Conclusion: Good syndrome should be considered in a patient with opportunistic infections and history of thymoma in the absence of human immunodeficiency virus. Atypical retinitis can occur in patients with Good syndrome and quantitative PCR is important for accurate diagnosis.     

Effect of Allergic Diseases on Keratoconus Severity

Purpose: To investigate the association between keratoconus (KC) and allergic diseases.

Methods: In a prospective age- and sex-matched case–-control study clinical data of 885 KC patients and 1526 controls were evaluated regarding the presence of various allergic diseases. Severity of KC and ophthalmic parameters of KC patients were compared between KC patients with and without allergic diseases.

Results: The prevalence of allergic diseases was significantly higher in KC patients. KC patients with vernal keratoconjunctivitis (VKC) or allergic conjunctivitis (AC) had significantly thinner and steeper corneas in comparison with non-allergic KC patients. Only VKC and AC were significantly associated with KC severity.

Conclusions: Patients with VKC or AC were at increased risk of KC. They had more severe KC and should be closely followed up and intensively treated.     

Leptospiral Uveitis: Usefulness of Clinical Signs as Diagnostic Predictors

Purpose: To analyze the diagnostic predictive ability of clinical variables.

Methods: Demographic and clinical variables of 172 serologically proven leptospiral uveitis patients were compared with 200 controls of non-leptospiral uveitis. Multiple logistic regression analysis identified diagnostic predictors. A receiver operating characteristic curve tested the performance of the model.

Results: Of all variables, male gender, farming as an occupation, and clinical features such as non-granulomatous panuveitis, hypopyon, and vitreous infiltration in the absence of retinochoroiditis constituted the predictive parameters, with the sensitivity and specificity of 86% and 90.7%, respectively.

Conclusions: Multiple logistic analysis detected clinically diagnostic predictors that can assist primary care ophthalmologists. Clinical diagnosis can further be confirmed by serology at tertiary care centers.     

Multimodal Imaging in Sympathetic Ophthalmia

Purpose: To show the current status of multimodal imaging and its role in supporting an early diagnosis of sympathetic ophthalmia.

Methods: The diagnosis is mainly clinical supported with ancillary investigations; mainly fluorescein angiography and others, including indocyanine angiography optical coherence tomography (OCT), OCT enhanced depth imaging, autofluorescence imaging, and ultrasonography.

Results: Various imaging modalities such as OCT, autofluorescence imaging and angiography are critical in the diagnosis and management of sympathetic ophthalmia. The clinician must make adequate use of such ancillary investigations in the management of the patients.

Conclusions: Sympathetic ophthalmia is a rare, bilateral inflammation of the uveal tract following penetrating trauma or surgery in one eye. The intraocular inflammation requires a prompt diagnosis so that the treatment can be initiated as early as possible.     

Repeat Conjunctival Biopsy after Immunomodulatory Therapy for Ocular Mucous Membrane Pemphigoid

Purpose: To evaluate whether conjunctival biopsy findings in patients with ocular mucous membrane pemphigoid (MMP) persist as positive or revert to negative following treatment with immunomodulatory therapy (IMT).

Methods: Patients with biopsy-proven MMP were treated with IMT for at least 2 years before undergoing repeat conjunctival biopsy for immunofluorescence microscopy. Their records were reviewed and findings evaluated to ascertain which patients’ biopsies showed antibody deposition on the conjunctival basement membrane.

Results: Following 2 years of IMT, conjunctival biopsies showed persistent antibody deposition in two patients, and were negative in four patients.

Conclusions: Conjunctival biopsies in patients with ocular MMP may show reversion to inactive disease following IMT. Post-treatment biopsy might be clinically useful as a means of evaluating the efficacy of therapy in this chronic disease.