Predictive Modeling of New-Onset Postoperative Diplopia Following Orbital Decompression for Thyroid Eye Disease.

PURPOSE: To identify risk factors for the development of new-onset, postoperative diplopia following orbital decompression surgery based on patient demographics, clinical exam characteristics, radiographic parameters, and surgical techniques. METHODS: We conducted a multi-center retrospective chart review of patients who underwent orbital decompression for thyroid eye disease (TED). Patient demographics, including age, gender, smoking history, preoperative exophthalmometry, clinical activity score (CAS), use of peribulbar and/or systemic steroids, and type of orbital decompression were reviewed. Postoperative diplopia was determined at a minimum of 3 months postoperatively and before any further surgeries. Cross-sectional area ratios of each extraocular muscle to orbit and total fat to orbit were calculated from coronal imaging in a standard fashion. All measurements were carried out using PACS imaging software. Multivariable logistic regression modeling was performed using Stata 14.2 (StataCorp, College Station, TX). RESULTS: A total of 331 patients without preoperative diplopia were identified. At 3 months postoperatively, 249 patients had no diplopia whereas 82 patients developed diplopia. The average postoperative follow-up was 22 months (range 3-156) months. Significant preoperative clinical risk factors for postoperative diplopia included older age at surgery, proptosis, use of peribulbar or systemic steroids, elevated clinical activity score, and presence of preoperative compressive optic neuropathy. Imaging findings of enlarged cross-sectional areas of each rectus muscle to the overall orbital area also conferred a significant risk of postoperative diplopia. Regarding surgical factors, postoperative diplopia was more common among those undergoing medial wall decompression, bilateral orbital surgery, and balanced decompression, whereas endoscopic medial wall decompression was found to be relatively protective. CONCLUSIONS: This study identifies risk factors associated with the development of diplopia following orbital decompression using multivariable data. This study demonstrates that several characteristics including age, clinical activity score, the cross-sectional muscle to orbit ratios, in addition to the type of orbital decompression surgery, are predictive factors for the development of new-onset postoperative diplopia.

Glaucoma and cataract surgery: two roads merging into one.

PURPOSE OF REVIEW: To discuss the increasing utilization of cataract extraction in the management of glaucoma and to highlight advances in surgical care that can promote synergistic treatment of these comorbid conditions. RECENT FINDINGS: Recent years have demonstrated significant advances in the management of glaucoma through the use of novel microinvasive glaucoma devices. Furthermore, an increased understanding of the role of cataract surgery in the treatment of various glaucomas warrants review. Nevertheless, cataract surgery in the glaucoma patient warrants specific preoperative, intraoperative, and postoperative planning to optimize visual function and quality of life while mitigating potential risk factors for adverse events. SUMMARY: Although the challenges of performing cataract extraction on glaucoma patients exist, the potential benefit to these patients is substantial. With attention to pre- and perioperative surgical planning and intraoperative technique, as well as with awareness and potential utilization of novel devices and treatment strategies, cataract extraction offers a unique platform for anatomical and functional improvement in this increasingly common cohort of patients.

CFH Y402H polymorphism is associated with elevated vitreal GM-CSF and choroidal macrophages in the postmortem human eye.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in people 50 years of age or older in developed countries. The homozygous CC genotype in the complement factor H (CFH) Y402H single nucleotide polymorphism (SNP; rs1061170) is widely recognized as a risk factor for the development of AMD. In this study, we examined vitreal levels of granulocyte macrophage colony-stimulating factor (GM-CSF), a hematopoietic cytokine, and macrophages in the choroid of postmortem human eyes genotyped for the CFH Y402H SNP. METHODS: Twenty-two pairs of postmortem, non-diseased, human donor eyes were obtained. The vitreous and retinal tissues of the left eyes were collected for GM-CSF level measurement and CFH Y402H genotyping, respectively. The right eyes were paraffin-embedded and sectioned for immunohistochemistry using a macrophage and microglia marker, CD68. Cell cultures of RPE cells were stimulated with complement C3a, C5a, 4-hydroxynonenal (HNE), or tumor necrosis factor alpha (TNF-α), and GM-CSF expression was measured with a suspension assay or quantitative PCR. RESULTS: Eyes genotyped with the CC or the CT risk variant of the CFH Y402H SNP showed significantly increased levels of GM-CSF in the vitreous compared to eyes with the protective TT variant (mean ± standard error of mean, 607.54±85.83 pg/ml or 656.32±15.20 pg/ml versus 286.69±81.96 pg/ml, p<0.05). The choroid of eye tissues genotyped with the CC variant showed higher levels of CD68 immunoreactivity than the tissues genotyped with the TT variant (p<0.05). The GM-CSF levels detected in the supernatant of RPE cells in culture treated with HNE or TNF-α were significantly higher compared to the non-treated control (145.88±5.06 pg/ml and 149.32±3.76 pg/ml versus 123.27±4.05 pg/ml, p<0.05). Furthermore, the gene expression of GM-CSF detected in the lysate of RPE cells stimulated with complement C3a or C5a showed significantly increased fold changes compared to the non-treated control (C3a: 2.38±0.31 fold, p<0.05; C5a: 2.84±0.54 fold, p<0.01). CONCLUSIONS: Our data showed a relationship between the CFH Y402H polymorphism and GM-CSF levels in the vitreous and accumulation of choroidal macrophages in the postmortem eye. These data suggest that the at-risk variant of the CFH gene may contribute to the dysregulation of proinflammatory cytokines locally in the eye.

Parainflammation associated with advanced glycation endproduct stimulation of RPE in vitro: implications for age-related degenerative diseases of the eye.

Age related macular degeneration (AMD) is one of the leading causes of blindness in Western society. A hallmark of early stage AMD are drusen, extracellular deposits that accumulate in the outer retina. Advanced glycation endproducts (AGE) accumulate with aging and are linked to several age-related diseases such as Alzheimer's disease, osteoarthritis, atherosclerosis and AMD. AGE deposits are found in drusen and in Bruch's membrane of the eye and several studies have suggested its role in promoting oxidative stress, apoptosis and lipofuscin accumulation. Recently, complement activation and chronic inflammation have been implicated in the pathogenesis of AMD. While AGEs have been shown to promote inflammation in other diseases, whether it plays a similar role in AMD is not known. This study investigates the effects of AGE stimulation on pro- and anti-inflammatory pathways in primary culture of human retinal pigment epithelial cells (RPE). Differential gene expression studies revealed a total of 41 up- and 18 down-regulated RPE genes in response to AGE stimulation. These genes fell into three categories as assessed by gene set enrichment analysis (GSEA). The main categories were inflammation (interferon-induced, immune response) and proteasome degradation, followed by caspase signaling. Using suspension array technology, protein levels of secreted cytokines and growth factors were also examined. Anti-inflammatory cytokines including IL10, IL1ra and IL9 were all overexpressed. Pro-inflammatory cytokines including IL4, IL15 and IFN-γ were overexpressed, while other pro-inflammatory cytokines including IL8, MCP1, IP10 were underexpressed after AGE stimulation, suggesting a para-inflammation state of the RPE under these conditions. Levels of mRNA of chemokine, CXCL11, and viperin, RSAD2, were up-regulated and may play a role in driving the inflammatory response via the NF-kB and JAK-STAT pathways. CXCL11 was strongly immunoreactive and associated with drusen in the AMD eye. The pathways and novel genes identified here highlight inflammation as a key response to AGE stimulation in primary culture of human RPE, and identify chemokine CXCL11 as putative novel agent associated with the pathogenesis of AMD.

Safety and efficacy of micropulse transscleral cyclophotocoagulation: 2-year follow-up in a tertiary Canadian centre.

OBJECTIVE: To describe the long-term results of patients undergoing micropulse cyclophotocoagulation (MPCPC). METHODS: Retrospective review of patients undergoing MPCPC with 1 surgeon between July 2016 and January 2017. Data collected included preoperative intraocular pressure (IOP), number of medications, daily acetazolamide use, and whether inferior, superior, or circumferential MPCPC was performed. This was assessed at postoperative week 1 and postoperative months 1, 3, 6, 12, 18, and 24. RESULTS: A total of 49 patients undergoing MPCPC with 2-year follow-up data was included. Ages ranged from 20 to 91 years (mean age, 69 years; 50% female). Following MPCPC, IOP was significantly lower at all points of follow-up (p < 0.05). At 2-year follow-up, the average IOP was 15 mm Hg (35% reduction). Six patients remained on acetazolamide (average daily dose, 333 mg). Average number of medications had decreased to 2.6 (p > 0.05). No significant structural complications occurred, but 53% required repeat MPCPC applications. The most common complication was failure requiring a secondary IOP-lowering surgical procedure. This occurred in 33% of patients. Subsequent glaucoma surgeries included gonioscopy-assisted transluminal trabeculotomy, iStent, Xen glaucoma implant, and Ahmed glaucoma valve. CONCLUSIONS: MPCPC was successful in reducing IOP in conjunction with a nonsignificant reduction in topical glaucoma medications. However, a large proportion of patients required repeat micropulse applications or invasive glaucoma surgery to achieve IOP control. These results suggest that the clinical efficacy of MPCPC may be lower than that reported in the literature.

Dural carotid cavernous fistula following hypertensive emergency.

A 58-year-old woman was referred to the outpatient ophthalmology clinic with progressive bilateral eye redness and vision loss. She had presented 2 weeks earlier with an episode of hypertensive emergency. CT angiography revealed bilateral superior ophthalmic vein (SOV) dilation, prompting further workup with a cerebral angiogram. Subsequent imaging revealed an indirect (type D) carotid-cavernous fistula (CCF) with venous drainage into both SOVs and cavernous sinuses. Successful treatment of the CCF with coil embolisation required interdisciplinary teamwork between ophthalmologists and interventional neuroradiologists. The patient made a substantial visual recovery following treatment.

Correlation in Severity Between Glaucoma and Erectile Dysfunction.

PURPOSE: To examine the association between open-angle glaucoma and erectile dysfunction (ED), and investigate the correlation in severity between these 2 conditions. METHODS: Cross-sectional study with patient questionnaire and retrospective chart review. A total of 167 male patients over 40 years of age who attended ophthalmology clinic visits in Vancouver, British Columbia, Canada, participated in the study by providing written consent and responding to the survey. Patients with previous radiation or surgical prostate treatment were excluded, leaving final sample sizes of 61 glaucoma patients and 67 control patients. Presence and severity of ED was determined using a validated patient questionnaire (the International Index of Erectile Function questionnaire). Presence of glaucoma was based on previous clinical diagnosis, and severity was graded based on visual field index using a 30-2 visual field test with the SITA Standard protocol. Bivariate analysis examined the presence of ED in glaucoma patients versus controls. Risk factors including dyslipidemia, diabetes, hypertension, and smoking were adjusted for using multiple logistic regression. The association between glaucoma and ED severity was assessed with correlation and scatterplot analysis. RESULTS: Glaucoma was found to be a significant risk factor for ED in our population, with an odds ratio of 2.58 (95% confidence interval, 1.15-5.83). Severity of glaucoma and ED were significantly correlated (r=0.365, P=0.007). CONCLUSIONS: Our results demonstrate that there is a positive association between the presence of ED and the diagnosis of glaucoma and a positive association between the severity of ED and the severity of glaucoma.