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.

A positive sentinel lymph node in periocular invasive squamous cell carcinoma: a case series.

PURPOSE: The aim of this article was to describe positive sentinel lymph node biopsy (SLNB) findings in patients with periocular invasive squamous cell carcinoma (SCC). METHODS: This was a retrospective chart review of 5 patients with invasive SCC of the periocular region who underwent SLNB and were found to have regional metastasis. RESULTS: All patients had large (2.0-4.3 cm) primary tumors with poor differentiation on pathology. In all 5 patients, SLNB was positive in the absence of other signs or evidence of regional or systemic metastasis. While tumor cells may drain to the preauricular or the submandibular basin, the preauricular lymph node was identified as the sentinel lymph node on lymphoscintigraphy in all 5 patients. With a positive sentinel lymph node, the results of SLNB changed the clinical staging and influenced subsequent treatment recommendations for each patient. We identified no complications related to SLNB including facial nerve damage, lymphedema, or allergic reaction to radioactive tracing material. CONCLUSIONS: In this series of patients with periocular invasive SCC, SLNB was well tolerated and uncovered regional metastasis in patients with no clinical signs of metastasis otherwise. The SLNB findings influenced subsequent oncologic management recommendations. The usefulness of SLNB for poorly differentiated SCC remains uncertain. Further research is necessary to establish the role of SLNB in periocular SCC.

Coup de sabre presenting with worsening diplopia and enophthalmos.

A middle-aged woman with a diagnosis of linear scleroderma and systemic sclerosis presented with an atrophic skin lesion of the forehead extending in the right orbit and progressive diplopia in the right gaze. On exam, she had enophthalmos with a small, manifest esotropia in the right gaze. Orbital MRI revealed fat atrophy of the right upper eyelid and orbit not previously described. Inflammation and progressive collagen fibrosis involving subcutaneous tissue, fat, and muscle secondary to linear scleroderma may result in enophthalmos and diplopia.

Short-term visual outcomes of Boston type 1 keratoprosthesis implantation.

PURPOSE: To report the short-term visual outcomes after keratoprosthesis implantation. DESIGN: Retrospective multi center case series (Wilmer Eye Institute and University of Rochester Eye Institute). PARTICIPANTS: One hundred twenty-two patients (126 eyes) with corneal diseases that were deemed ineligible to receive donor corneal transplants. INTERVENTION: Patients underwent a Boston type I keratoprosthesis procedure for visual rehabilitation. MAIN OUTCOME MEASURES: The medical records of the patients were reviewed to assess intraoperative and postoperative complications, uncorrected and best-corrected visual acuity, as well as the degree of refractive error at various time points. RESULTS: One hundred four patients (82.5%) achieved improved vision within 6 months after surgery. An overwhelming majority of those patients who had improved vision had a manifest refraction of plano. The mean spherical refractive error was -0.57 diopters (D) and mean astigmatism was 0.10 D. Cumulatively, 7.1% patients achieved their best-corrected vision at 1 day, 24.6% at 1 week, and 70.6% at 3 months. The patients who achieved their best-corrected visual acuity after the first 3-month period most often were the ones who required multiple surgeries owing to preexisting or postoperative complications. CONCLUSIONS: Boston keratoprosthesis seems to provide rapid visual recovery with excellent uncorrected acuity in the early postoperative period. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Sinus opacification associated with exacerbation of thyroid eye disease.

PURPOSE: To describe the association of sinus opacification with exacerbation of thyroid eye disease. Three cases followed orbital decompression performed when disease was quiescent and one case occurred without prior orbital or sinus surgery. DESIGN: Retrospective observational case series. METHODS: Four patients' charts were retrospectively reviewed. RESULTS: Three patients with thyroid eye disease (TED), whose ophthalmopathy was stable after orbital decompression surgery, experienced recurrence of TED signs and symptoms after development of sinus inflammation. The fourth patient with TED did not have orbital surgery but presented with unilateral ophthalmopathy and ipsilateral sinus opacification. CONCLUSION: Paranasal sinus disease can exacerbate TED, possibly through a nonspecific inflammatory response. Minimizing inflammation proximal to the orbit may afford some protection against progression of the orbital process occurring in TED.

Atypical Presentation of Acute Angle-Closure Glaucoma in Maroteaux-Lamy Mucopolysaccharidosis with Patent Prophylactic Laser Peripheral Iridotomy: A Case Report.

INTRODUCTION: Maroteaux-Lamy syndrome (MLS) is a rare progressive condition characterized by inflammation and scarring of multiple organs. Ocular complications caused by anterior segment abnormalities commonly cause visual impairment in MLS. Angle-closure glaucoma is one such complication, but there are limited data on presentation, workup, and management of this condition. CASE PRESENTATION: This case report describes an atypical presentation of acute angle-closure glaucoma in a patient with MLS despite a prior prophylactic laser peripheral iridotomy-which would typically prevent an acute angle-closure attack-that was patent and intact at the time of angle closure. DISCUSSION: Because of severe congenital anterior segment crowding, high axial hyperopia, and constant accommodative demand in patients with MLS, we recommend performing two prophylactic laser peripheral iridotomies simultaneously in the same eye instead of one. The mechanism for this indication differs from that in patients at risk of acute angle-closure glaucoma because of lens zonulopathy alone. We hope that this case report may help prevent vision loss and optimize quality of life in patients with MLS who may be wheelchair-bound but are typically high functioning with normal intelligence.

Outcome of primary trabeculotomy ab interno (Trabectome) surgery in patients with steroid-induced glaucoma.

To determine the efficacy and safety of Trabectome surgery on patients with steroid response, ranging from ocular hypertension refractory to maximal medical therapy to the development of steroid-induced glaucoma.A nonrandomized, nonblinded, retrospective study of 20 subjects with steroid response was conducted. All 20 eyes underwent Trabectome surgery alone. Nine subjects had steroid response with unremarkable visual field, 3 had mild steroid-induced glaucoma, and 8 had advanced steroid-induced glaucoma. Outcome measures included intraocular pressure (IOP), number of glaucoma medications, need for secondary glaucoma surgery, and steroid regimen. Mann-Whitney U test was used to compare postoperative IOP and number of medications to preoperative IOP and number of medications. Kaplan-Meier was used for survival analysis, and success was defined as: IOP reduced by 20% or more on any 2 consecutive visits after 3 months; IOP ≤21 mm Hg on any 2 consecutive visits after 3 months; and no secondary glaucoma surgery.The average preoperative IOP was 33.8 ±â€Š6.9 mm Hg and average preoperative glaucoma medication usage was 3.85 ±â€Š0.75 medications. At 12 months, the IOP was reduced to 15.00 ±â€Š3.46 mm Hg (P = 0.03) and glaucoma medication was reduced to 2.3 ±â€Š1.4 (P < 0.01). The survival rate at 12 months was 93%. At 12 months, 10 patients were continued on their preoperative steroid treatments, 5 were on tapered steroid treatments, and 5 had ceased steroid treatments entirely. One patient required secondary glaucoma surgery (glaucoma drainage device). No other complications were noted.The Trabectome procedure is safe and highly effective for steroid-response glaucoma, even in the context of continued steroid treatment.

Results of Trabectome Surgery Following Failed Glaucoma Tube Shunt Implantation: Cohort Study.

To evaluate the safety and efficacy of Trabectome after failed tube shunt surgery.Twenty patients with prior failed tube shunt surgery who underwent Trabectome alone were included. All patients had at least 3 months of follow-up. Outcomes measured included intraocular pressure (IOP), glaucoma medications, and secondary glaucoma surgeries. The success for Kaplan-Meier survival analysis is defined as IOP ≤21 mm Hg, IOP reduced by at least 20% from preoperative IOP, and no secondary glaucoma surgery.Mean preoperative IOP was 23.7 ± 6.4 mm Hg and mean number of glaucoma medications was 3.2 ± 1.5. At 12 months, IOP was reduced to 15.5 ± 3.2 mm Hg (P = 0.05) and number of medications was reduced to 2.4 ± 1.5 (P = 0.44). Survival rate at 12 months was 84% and 3 patients required additional glaucoma surgery with 15 patients reaching 12 months follow-up. Other than failure of IOP control and transient hypotony (IOP < 3 mm Hg) day 1 in 2 cases, there were no adverse events.Trabecular bypass procedures have traditionally been considered an approach appropriate for early-to-moderate glaucoma; however, our study indicates benefit in refractory glaucoma as well. Eyes that are prone to conjunctival scarring and hypertrophic wound healing, such as those who have failed tube shunt surgery, may benefit from procedures that avoid conjunctival incision such as Trabectome. This study indicates potential benefits in this patient population.Trabectome was safe and effective in reducing IOP at 1-year follow-up in patients with prior failed tube shunt surgery, but not effective in reducing medication reliance in these patients.

Reduction in mean deviation values in automated perimetry in eyes with multifocal compared to monofocal intraocular lens implants.

PURPOSE: To evaluate differences in mean deviation values in automated perimetry in healthy eyes with multifocal compared to monofocal intraocular lens (IOL) implants. DESIGN: Prospective, age-matched, comparative analysis. SETTING: Single-center, tertiary referral academic practice. PATIENT POPULATION: A total of 37 healthy eyes in 37 patients with bilateral multifocal (n=22) or monofocal (n=15) IOL implants were studied. INTERVENTION/OBSERVATION PROCEDURE: Humphrey Visual Field 10-2 testing was performed on all patients. MAIN OUTCOME MEASURES: Mean deviation (MD) and pattern standard deviation (PSD) numerical values were evaluated and compared between groups. RESULTS: The average MD was -2.84 dB (SD 2.32) for the multifocal IOL group and -0.97 dB (SD 1.58) for the monofocal IOL group (P=.006). There was no significant difference in PSD between the 2 groups (P=.99). Eyes that had the visual field 10-2 testing≥6 months from time of IOL placement showed no improvement in MD when compared to eyes that were tested within 6 months from IOL placement. CONCLUSION: Multifocal IOL implants cause significant nonspecific reduction in MD values on Humphrey Visual Field 10-2 testing that does not improve with time or neuroadaptation. Multifocal IOL implants may be inadvisable in patients where central visual field reduction may not be tolerated, such as macular degeneration, retinal pigment epithelium changes, and glaucoma.

A safe Nd:YAG retroprosthetic membrane removal technique for keratoprosthesis.

PURPOSE: To describe a technique for Nd:YAG laser photodiscission of retroprosthetic membrane (RPM) in keratoprosthesis patients that minimizes damage to the optic. METHODS: Prospective review of Boston type I keratoprosthesis patients at 1 site who received Nd:YAG treatment for RPM from 2005 to 2009. Outcomes were based on slit-lamp examination of the optic immediately after YAG treatment, tactile intraocular pressure at follow-up, and complications from the outpatient procedure. RESULTS: The incidence of RPM was 24.1% (39 of 162 eyes). Of 26 RPM eyes receiving YAG treatment, 18 had 1 YAG treatment, 6 had multiple YAG treatments, and 2 had surgical excision despite multiple YAG treatments because of membrane thickness. All 26 eyes had no intraoperative complications, no damage to the optic from slit-lamp examination, and soft tactile intraocular pressures. CONCLUSION: Based on the office procedures from our patient base, YAG retroprosthetic membranectomy using a peripheral "can-opener" approach is effective and safe with no evident damage to the optic.

Characterization of retinal and blood mitochondrial DNA from age-related macular degeneration patients.

PURPOSE: To determine mitochondrial (mt)DNA variants in AMD and age-matched normal retinas. METHODS: Total DNA was isolated from retinas (AMD, n = 13; age-matched normal, n = 13), choroid (AMD, n = 3), and blood (AMD, n = 138; normal, n = 133). Long-extension-polymerase chain reaction amplified the full-length ( approximately 16.2 kb) mtDNA genome. Retinal mtDNA was sequenced for nucleotide variants and length heteroplasmy. Pyrosequencing was performed on heteroplasmic mtDNA. PCR amplification and enzyme digestions were used to analyze for nucleotide changes. RESULTS: Retinal mtDNA had a greater number of rearrangements and deletions than did blood mtDNA in normal samples (9.3 +/- 1.78 vs. 3 +/- 1.18, P = 0.019), and AMD samples (14.33 +/- 1.96 vs. 5.2 +/- 0.80, P = 0.0031. Five (55%) of 9 AMD patients had unreported SNPs, and 2 (16.6%) of 12 of the normal group did. The mtDNA coding region had 20 SNPs that produced amino acid changes. The noncoding MT-Dloop region had nucleotide heteroplasmy and length heteroplasmy. There were more SNPs per person in the AMD population than in the older (P = 0.003) and younger (P = 0.05) normal subjects. The C12557T (T-I) in the MT-ND5 gene was present in two AMD subjects (2/138) but was absent in the normal (0/133). Common mutations for Leber's hereditary optic neuropathy (LHON: G11778A; T14484C; and G3460A) were not present in AMD samples. CONCLUSIONS: AMD subjects have high levels of large mtDNA deletions/rearrangements in the retinas, unreported and amino acid-changing SNPs in the coding genome, and a greater number of SNPs per person in the noncoding MT-Dloop region. These mtDNA variants could diminish energy production efficiency, alter the mtDNA copy numbers and/or impact transcription in AMD retinas.

A rat model of radiofrequency ablation of trigeminal innervation via a ventral approach with stereotaxic surgery.

Neurotrophic keratopathy (NK), a consequence of sensory denervation of the cornea, must be better understood in order to develop new approaches to therapy. The purpose of this study was to create a rat model for neurotrophic keratopathy by denervating the trigeminal nerve through a ventral approach with stereotaxic surgery. Stereotaxic coordinates were measured in 46 male Sprague Dawley rat cadavers for localization of V1. After further refining the coordinates in nine live animals, radiofrequency ablation was chosen as an effective method of disrupting the innervation to the cornea. Fifty-two live rats were treated with radiofrequency ablation to define the anatomical localization of the lesion by utilizing gross and histopathological studies. A gross lesion of the trigeminal nerve and/or ganglion was observed in 47 (90%) of the 52 animals. Histopathological studies revealed that all 52 animals had anatomical damage of the trigeminal innervation to the eye. Low mortality and little morbidity were observed in these animals. We have developed a rat model for neurotrophic keratopathy that is simple to produce, accurate in creating a lesion by utilizing stereotaxic techniques combined with radiofrequency ablation, and successful in decreasing morbidity and mortality.