M. T. Andreoli

Treatment of esthesioneuroblastoma: a 16-year meta-analysis of 361 patients.

This study reviews the published outcomes related to surgical (open, endoscopic, and endoscopic‐assisted) and nonsurgical treatment for esthesioneuroblastoma.

Low Rate of Endophthalmitis in a Large Series of Open Globe Injuries

PURPOSE To determine the percentage of patients in whom endophthalmitis developed after open globe injury. DESIGN Retrospective, noncomparative, consecutive case series. METHODS Charts of all patients (675 in total) treated surgically for open globe injury at the Massachusetts Eye and Ear Infirmary (MEEI) between January 1, 2000 and July 31, 2007 were reviewed. Cases with at least 30 days of follow-up were included in statistical analyses (558 in total). A standardized treatment protocol was used in all cases. Intravenous vancomycin and ceftazidime were started on admission and were stopped after 48 hours. Patients were discharged on topical antibiotics, corticosteroids, and cycloplegia. Surgical repairs were performed by the chief of trauma, a full-time position rotating yearly, who is on call for all open globe trauma. Data collection variables included timing of injury and repair, mechanism of injury, details of surgical repair, and details of follow-up such as duration, presence of complications, and vision. A primary outcome measure of endophthalmitis and secondary outcome measure of risk factors for endophthalmitis were studied. RESULTS During 7.5 years, 675 open globe injuries were treated at MEEI. Of these, 558 had at least 30 days of follow-up (mean, 11 months) and were used in statistical analyses. The overall percentage of endophthalmitis was 0.9% (3 culture-positive cases and 2 culture-negative cases). Four of the 5 cases achieved final acuity of 20/80 or better. Risk factors for endophthalmitis included intraocular foreign body (P = .03; odds ratio, 7.52) and primary intraocular lens placement (P = .05). CONCLUSIONS A standardized protocol including surgical repair by a dedicated eye trauma service and 48 hours of intravenous antibiotics was associated with a posttraumatic endophthalmitis percentage of less than 1%.

The NEI/NCBI dbGAP database: Genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration

BackgroundTo examine if the significantly associated SNPs derived from the genome wide allelic association study on the AREDS cohort at the NEI (dbGAP) specifically confer risk for neovascular age-related macular degeneration (AMD). We ascertained 134 unrelated patients with AMD who had one sibling with an AREDS classification 1 or less and was past the age at which the affected sibling was diagnosed (268 subjects). Genotyping was performed by both direct sequencing and Sequenom iPLEX system technology. Single SNP analyses were conducted with McNemars Test (both 2 × 2 and 3 × 3 tests) and likelihood ratio tests (LRT). Conditional logistic regression was used to determine significant gene-gene interactions. LRT was used to determine the best fit for each genotypic model tested (additive, dominant or recessive).ResultsBefore release of individual data, p-value information was obtained directly from the AREDS dbGAP website. Of the 35 variants with P < 10-6 examined, 23 significantly modified risk of neovascular AMD. Many variants located in tandem on 1q32-q22 including those in CFH, CFHR4, CFHR2, CFHR5, F13B, ASPM and ZBTB were significantly associated with AMD risk. Of these variants, single SNP analysis revealed that CFH rs572515 was the most significantly associated with AMD risk (P < 10-6). Haplotype analysis supported our findings of single SNP association, demonstrating that the most significant haplotype, GATAGTTCTC, spanning CFH, CFHR4, and CFHR2 was associated with the greatest risk of developing neovascular AMD (P < 10-6). Other than variants on 1q32-q22, only two SNPs, rs9288410 (MAP2) on 2q34-q35 and rs2014307 (PLEKHA1/HTRA1) on 10q26 were significantly associated with AMD status (P = .03 and P < 10-6 respectively). After controlling for smoking history, gender and age, the most significant gene-gene interaction appears to be between rs10801575 (CFH) and rs2014307 (PLEKHA1/HTRA1) (P < 10-11). The best genotypic fit for rs10801575 and rs2014307 was an additive model based on LRT. After applying a Bonferonni correction, no other significant interactions were identified between any other SNPs.ConclusionThis is the first replication study on the NEI dbGAP SNPs, demonstrating that alleles on 1q, 2q and 10q may predispose an individual to AMD.

Enucleation for open globe injury.

PURPOSE To report the experience of enucleation after open globe at an ophthalmic trauma referral center. DESIGN Retrospective, observational study. METHODS In an ophthalmic trauma referral center the charts of all patients having suffered an open globe injury between January 1, 2000 and June 30, 2007 were reviewed. Variables assessed were age, gender, type of injury (rupture or laceration [penetrating, intraocular foreign body, or perforating]), ocular trauma score, visual acuity, subsequent enucleation, indication for and timing of enucleation, presence of sympathetic ophthalmia, and length of follow-up. RESULTS Among 660 open globe injuries, 55 have undergone enucleation (including 4 eviscerations), 11 primarily and 44 secondarily. Eyes with ruptures were significantly more likely to be enucleated than those with injuries attributable to lacerations (P < .001). The most common reason for secondary enucleation was a blind, painful eye. Two patients (0.3%) developed sympathetic ophthalmia and have maintained good vision in the sympathizing eye. CONCLUSIONS The vast majority of open globes can be repaired without requiring primary enucleation. Secondary enucleation is most commonly carried out for pain. Eyes with no light perception can be closely observed if the patient chooses.

Comprehensive analysis of complement factor H and LOC387715/ARMS2/HTRA1 variants with respect to phenotype in advanced age-related macular degeneration.

PURPOSE To examine the interaction of genotypic variation of 16 single-nucleotide polymorphisms (SNP) in the complement factor H (CFH) and LOC387715/ARMS2/HTRA1 loci with clinical characteristics of age-related macular degeneration (AMD). DESIGN Retrospective cohort study. METHODS Eighty-four patients with neovascular AMD were genotyped using direct sequencing or Sequenom iPLEX technology. The Fisher exact test, Cochran-Mantel-Haenszel statistics, and Mann-Whitney U test were used to assess the effect of each SNP with respect to the following phenotypic manifestations: age at diagnosis, gender, affected eye, study and fellow eye visual acuity at diagnosis and at last follow-up, study eye best acuity during follow-up, presence of large drusen and retinal pigment epithelium (RPE) hyperpigmentation in study and fellow eye, choroidal neovascularization (CNV) angiographic subtype (classic vs occult), CNV size, presence of wet AMD in fellow eye, presence of dry AMD in fellow eye, and smoking history. RESULTS Only SNPs in the LOC387715/ARMS2/HTRA1 (10q26) region were associated with disease phenotypes. The polymorphisms rs10664316 and rs1049331 were associated with a decreased risk of poor visual acuity during follow-up and at diagnosis; rs2672598 and rs2293870 were associated with a decreased risk of RPE hyperpigmentation; rs10664316 was associated with a decreased risk of RPE hyperpigmentation with large drusen in the study eye, but an increased risk of large drusen in the fellow eye; rs11200638 was associated with an increased risk of larger CNV; rs10490924 and rs11200638 were associated with younger age of diagnosis. CONCLUSIONS Several polymorphisms examined in the LOC387715/ARMS2/HTRA1 locus, but none in the CFH region, correlated with specific phenotypic attributes of AMD.

Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration

Vitamin D has been shown to have anti-angiogenic properties and to play a protective role in several types of cancer, including breast, prostate and cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective for risk of a number of conditions, including cardiovascular disease and chronic kidney disease, as well as numerous autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study performed by Parekh et al. was the first to suggest a role for vitamin D in age-related macular degeneration (AMD) and showed a correlation between reduced serum vitamin D levels and risk for early AMD. Based on this study and the protective role of vitamin D in diseases with similar pathophysiology to AMD, we examined the role of vitamin D in a family-based cohort of 481 sibling pairs. Using extremely phenotypically discordant sibling pairs, initially we evaluated the association of neovascular AMD and vitamin D/sunlight-related epidemiological factors. After controlling for established AMD risk factors, including polymorphisms of the genes encoding complement factor H (CFH) and age-related maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1), and smoking history, we found that ultraviolet irradiance was protective for the development of neovascular AMD (p = 0.001). Although evaluation of serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) was higher in unaffected individuals than in their affected siblings, this finding did not reach statistical significance.Based on the relationship between ultraviolet irradiance and vitamin D production, we employed a candidate gene approach for evaluating common variation in key vitamin D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family 24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1) in this same family-based cohort. Initial findings were then validated and replicated in the extended family cohort, an unrelated case-control cohort from central Greece and a prospective nested case-control population from the Nurses Health Study and Health Professionals Follow-Up Studies, which included patients with all subtypes of AMD for a total of 2,528 individuals. Single point variants in CYP24A1 (the gene encoding the catabolising enzyme of the vitamin D pathway) were demonstrated to influence AMD risk after controlling for smoking history, sex and age in all populations, both separately and, more importantly, in a meta-analysis. This is the first report demonstrating a genetic association between vitamin D metabolism and AMD risk. These findings were also supplemented with expression data from human donor eyes and human retinal cell lines. These data not only extend previous biological studies in the AMD field, but further emphasise common antecedents between several disorders with an inflammatory/immunogenic component such as cardiovascular disease, cancer and AMD.

Characteristics and Outcomes of Work-Related Open Globe Injuries

PURPOSE To evaluate the characteristics and outcomes of patients treated for open globe injuries sustained at work and to compare these results to patients injured outside of work. DESIGN Retrospective chart review of 812 consecutive patients with open globe injuries treated at the Massachusetts Eye and Ear Infirmary between 1999 and 2008. METHODS A total of 146 patients with open globe injuries sustained at work were identified and their characteristics and outcomes were compared with the rest of the patients in the database. RESULTS Of the patients injured at work, 98% were men, and the average age of the patients was 35.8 years (17-72 years). The most common mechanism of injury was penetrating trauma (56%); 38 patients examined had intraocular foreign bodies (IOFB). Nine work-related open globe injuries resulted in enucleation. There was a higher incidence of IOFBs (P = .0001) and penetrating injuries (P = .0005) in patients injured at work. Both the preoperative (P = .0001) and final best-corrected visual acuity (P = .0001) was better in the work-related group. The final visual acuity was better than 20/200 in 74.1% of cases of work-related open globe injuries. However, there was no difference observed in the rate of enucleations (P = .4). CONCLUSIONS Work-related injuries can cause significant morbidity in a young population of patients. Based on average patient follow-up and final visual acuity, those injured at work do at least as well as, if not potentially better than, those with open globe injuries sustained outside of work. While the statistically higher rate of IOFB in the work population is not surprising, it does emphasize the importance of strict adherence to the use of eye protection in the workplace.

Surgical Rehabilitation of the Open Globe Injury Patient

PURPOSE To describe the long-term surgical course of patients with open globe injury. DESIGN Retrospective case series. METHODS Patients with open globe injuries (848 in total) treated surgically at the Massachusetts Eye and Ear Infirmary between 2000 and 2009 were retrospectively reviewed. Data from presentation, initial repair, and follow-up surgery were analyzed. RESULTS Among 848 injuries, 1415 surgical procedures were performed. The mean follow-up time was 19.7 months, including 6017 visits. On average, patients required 1.7 surgeries and 7.1 follow-up visits. Factors predicting follow-up surgery included more severe ocular trauma score, worse prerepair visual acuity, retinal hemorrhage, anterior vitrectomy at primary repair, pars plana vitrectomy at primary repair, and lensectomy at primary repair. Patients with zone II injury, hemorrhagic choroidal detachment, and a history of previous ocular surgery tended to require follow-up surgery less frequently. Patients requiring a second surgery tended to have worse visual acuity at presentation and postrepair. Postoperative visual outcomes were worse for patients who underwent vitreoretinal follow-up surgery, likely because of mechanism of injury. Variables associated with inferior visual outcome were worse prerepair visual acuity, postoperative afferent pupillary defect (APD), old age, scleral laceration, and retinal detachment. CONCLUSION Open globe injuries require significant surgical follow-up. Patients requiring multiple operations tended to have worse postoperative visual acuity. Patients who underwent vitreoretinal surgery had overall worse visual outcomes. While the first year of surveillance appears to be pivotal in the course of an open globe injury, these patients can expect long-term care from comprehensive and subspecialty ophthalmologists.

Malignant eccrine spiradenoma: a meta-analysis of reported cases

BACKGROUND Malignant eccrine spiradenoma is an aggressive sweat gland tumor with poorly understood behavior and no currently accepted therapeutic regimen. METHODS An individual patient data meta-analysis with Kaplan–Meier survival curves was performed on 72 reported cases of malignant eccrine spiradenoma. RESULTS In 35 patients with no distant metastasis, local resection resulted in 100% disease-free survival. Of 7 patients with lymph node but no distant metastasis treated with surgical resection and lymph node dissection, 6 patients remained disease-free at final follow-up evaluation. For the 24 cases with confirmed distant metastatic disease, patient survival did not significantly differ between local resection and surgery with adjuvant chemoradiotherapy (P = .8763). CONCLUSIONS Heightened awareness is recommended among surgeons likely to treat this entity. An aggressive surgical approach is supported in the absence of metastasis. When lymph nodes are not clinically involved, sentinel node may have a role followed by lymph node dissection in patients with a positive node.

Geriatric Traumatic Open Globe Injuries

PURPOSE To characterize the pattern of ocular trauma in the geriatric population. DESIGN Retrospective, comparative case series. PARTICIPANTS Eight hundred forty-six consecutive patients comprising 848 open globe injuries, of which 166 injuries occurred in geriatric patients (defined as 65 years old or older at the time of injury), with the remaining patients serving as control subjects. METHODS Charts of open globe injuries (848 in total) treated surgically at the Massachusetts Eye and Ear Infirmary between January 2000 and April 2009 were retrospectively reviewed. MAIN OUTCOME MEASURES Ocular Trauma Score, age, gender, mechanism of injury, zone of injury, site of injury, time of day, visual acuity at presentation, and best post-repair visual acuity were analyzed. RESULTS Of 848 open globe injuries, 166 occurred in the geriatric population. The mean patient age in the geriatric group was 79.8 years. Females comprised most (58%) of this subpopulation. The most common mechanisms of injury were fall (65%), blunt trauma (16%), and motor vehicle accident (6%). The geriatric traumas tended to happen in late morning or late at night. There were no cases of endophthalmitis and fewer instances of enucleation in this group. The median raw Ocular Trauma Score was 47 in the geriatric population, compared with 70 in the younger subset (P < 0.0001). The injuries more often were in zones II and III in the geriatric population compared with the nongeriatric population (P < 0.0001). The geriatric patients were much more likely to have undergone previous intraocular surgery (P < 0.0001), which consisted of primarily cataract procedures. Visual acuity at presentation was significantly worse in the geriatric population than the nongeriatric population (P<0.0001). Similarly, the best postoperative visual acuity was worse in the elderly group than the younger group (P < 0.0001). CONCLUSIONS The elderly represent a unique, yet neglected ocular trauma population. The pattern of ophthalmic injury and outcome differs greatly between the geriatric and nongeriatric populations. A better understanding of these injuries is necessary to improve prevention and treatment strategies for potentially devastating open globe injuries in this susceptible population.