Thyroid Eye Disease.

Thyroid eye disease (TED), an autoimmune inflammatory disorder of the orbit, presents with a potential array of clinical sequelae. The pathophysiology behind TED has been partially characterized in the literature. There remain certain elusive mechanisms welcoming of research advances. Disease presentation can vary, but those that follow a characteristic course start mild and increase in severity before plateauing into an inactive phase. Diagnosis and evaluation include careful physical examination, targeted laboratory work up, appropriate imaging studies, and tailored treatment regimens. Special consideration may apply to certain populations, such as pediatric and pregnant patients.

Angiolymphoid Hyperplasia with Eosinophilia with Clinical Presentation Concerning for Juvenile Temporal Arteritis.

A 20-year-old boy presented with a mass superotemporal to the right eyebrow of 1 month's duration without a history of recent trauma. Complete examination and workup, including laboratory analysis, Doppler ultrasound imaging, and magnetic resonance imaging, suggested a diagnosis of juvenile temporal arteritis. Excisional biopsy and histopathology contradicted the preoperative workup and yielded the final diagnosis of angiolymphoid hyperplasia with eosinophilia, a rare eosinophilic dermatosis of unknown etiology. This case highlights the need for better characterization of temporal vascular tumors in the pediatric population.

Pulmonary Adenocarcinoma Metastatic to Periocular Skin and Orbital Tissue Presenting as Orbital Cellulitis.

A 56-year-old man presented with a periorbital subcutaneous mass and ipsilateral visually significant orbital inflammation that was refractory to broad-spectrum antibiotics. Orbitotomy with biopsy revealed the diagnosis of metastatic lung cancer, and the patient was initiated on systemic chemotherapy and adjuvant radiation. This is the first report of pulmonary adenocarcinoma metastatic simultaneously to the periocular cutaneous and intraorbital soft tissues. Atypical periorbital and orbital inflammation may be the initial presentation of occult malignancy and require a high index of suspicion and tissue biopsy for diagnosis and life-saving management.

Acute Sterile Canaliculitis: A Case Report and Review of the Literature.

A 53-year-old male developed secondary canaliculitis after undergoing nasolacrimal intubation with a silicone stent. Negative cultures, symptoms refractory to antibiotics, and rapid resolution after stent removal suggest an immune reaction as the mechanism of canaliculitis. This case raises awareness of noninfectious hypersensitivity or hypersensitivity-like reactions as a potential acute or subacute complication of nasolacrimal stenting.

Necrotizing Orbital Cellulitis Secondary to Odontogenic Streptococcus constellatus.

A 69-year-old woman with orbital cellulitis secondary to odontogenic Streptococcus constellatus was transferred to the authors' institution for surgical management of infection refractory to intravenous antibiotics. She underwent debridement with preservation of the globe, recovering full motility. Visual recovery was limited by optic nerve ischemia. This case supports the importance of urgent surgical drainage in necrotizing orbital infections secondary to odontogenic Streptococcus constellatus.

Comparison of Fasanella-Servat and Small-Incision Techniques for Involutional Ptosis Repair.

PURPOSE: To compare the results of the classic Fasanella-Servat internal approach to the newer, small-incision external approach in the repair of involutional ptosis. METHODS: Retrospective review identified 93 patients (104 surgical procedures) at Northwestern Ophthalmology from June 2005 until October 2011 who underwent either the Fasanella-Servat or the small-incision approaches for involutional ptosis repair. Change in vertical palpebral fissure measurement, change in marginal reflex distance 1 (MRD1) measurement, patient satisfaction, surgical complications, operating time, and postoperative pain were compared between groups. RESULTS: Of the 93 patients, most were female with an average age of 69 years. Of the procedures, 48% were small incision and 52% were Fasanella-Servat approaches. Average postoperative follow up was 34.0 days. Vertical palpebral fissure height increased an average of 3.36 mm (±1.15) in the Fasanella-Servat group and 2.74 mm (±1.18) in the small-incision group (p = 0.003). Preoperative vertical palpebral fissure height was lower in the Fasanella-Servat group, but postoperative vertical palpebral fissure height was similar between the 2 groups (p=0.3). MRD1 increased an average of 3.42 mm (±0.86) in the Fasanella-Servat group and 2.68 mm (±0.93) in the small-incision group (p < 0.01). Preoperative MRD1 was lower in the Fasanella-Servat group, but postoperative MRD1 was similar between the 2 groups (p = 0.15). Average operating time was 53 minutes (±16) in the small-incision group and 27 minutes (±6) in the Fasanella-Servat group (p < 0.01). There were no surgical complications in either group with equivalent patient satisfaction between the 2 groups. More patients reported postoperative pain in the Fasanella-Servat group (p < 0.0001). CONCLUSIONS: Both the Fasanella-Servat and small-incision approaches lead to good surgical outcomes with equivalent patient satisfaction, although the Fasanella-Servat approach provides a shorter average operating time with satisfactory postoperative MRD1.

A Validated Phenotyping Algorithm for Genetic Association Studies in Age-related Macular Degeneration.

Age-related macular degeneration (AMD), a multifactorial, neurodegenerative disease, is a leading cause of vision loss. With the rapid advancement of DNA sequencing technologies, many AMD-associated genetic polymorphisms have been identified. Currently, the most time consuming steps of these studies are patient recruitment and phenotyping. In this study, we describe the development of an automated algorithm to identify neovascular (wet) AMD, non-neovascular (dry) AMD and control subjects using electronic medical record (EMR)-based criteria. Positive predictive value (91.7%) and negative predictive value (97.5%) were calculated using expert chart review as the gold standard to assess algorithm performance. We applied the algorithm to an EMR-linked DNA bio-repository to study previously identified AMD-associated single nucleotide polymorphisms (SNPs), using case/control status determined by the algorithm. Risk alleles of three SNPs, rs1061170 (CFH), rs1410996 (CFH), and rs10490924 (ARMS2) were found to be significantly associated with the AMD case/control status as defined by the algorithm. With the rapid growth of EMR-linked DNA biorepositories, patient selection algorithms can greatly increase the efficiency of genetic association study. We have found that stepwise validation of such an algorithm can result in reliable cohort selection and, when coupled within an EMR-linked DNA biorepository, replicates previously published AMD-associated SNPs.

Management of the eye in facial paralysis.

Facial nerve palsy, whether the cause is idiopathic, or following such insults as surgery, trauma, or malignancy, places the health of the ocular surface at risk. Reduced or absent orbicularis oculi function results in lagophthalmos and exposure of the cornea, which is exacerbated by eyelid malposition. Management of the exposure keratopathy is paramount to prevent corneal breakdown, scarring, and permanent vision loss. Significant exposure keratopathy can be complicated by loss of corneal sensation, leading to a neurotrophic corneal ulcer. Initial management consists of artificial tear drops and ointment for corneal lubrication and strategies to address the lagophthalmos. Once the condition of the ocular surface has been stabilized, a variety of surgical treatment options are available depending on the severity and persistence of eyelid and ocular findings. The most common surgical options include temporary or permanent tarsorrhaphy for lagophthalmos, upper eyelid weight placement for retraction, and lateral canthoplasty with or without a middle lamellar spacer for lower eyelid retraction. External eyelid loading is a good option in patients who are poor surgical candidates or who have a known temporary palsy of short duration. The goal of all such procedures must be protection of the ocular surface through optimization of eyelid position.

Reticular macular disease is associated with multilobular geographic atrophy in age-related macular degeneration.

PURPOSE: To investigate the incidence of reticular macular disease (RMD), a subphenotype of age-related macular degeneration, in multilobular geographic atrophy (GA) and its relation to GA progression. METHODS: One hundred and fifty-seven eyes of 99 subjects with age-related macular degeneration, primary GA, and good quality autofluorescence, and/or infrared images were classified into unilobular GA (1 lesion) or multilobular GA (≥ 2 distinct and/or coalescent lesions). Thirty-four subjects (50 eyes) had serial imaging. The authors determined the spatiotemporal relationships of RMD to GA and GA progression rates in five macular fields. RESULTS: 91.7% eyes (144 of 157) had multilobular GA, 95.8% of which exhibited RMD. In subjects with serial imaging, the mean GA growth rate significantly differed between the unilobular and multilobular groups (0.40 vs. 1.30 mm2/year, P < 0.001). Of the macular fields in these eyes, 77.1% of fields with RMD at baseline showed subsequent GA progression, while 53.4% of fields without RMD showed progression (P < 0.001). Percentage of fields with RMD significantly correlated with GA progression rate (P = 0.01). CONCLUSION: Autofluorescence and infrared imaging demonstrates that RMD is nearly always present with multilobular GA in age-related macular degeneration. Furthermore, GA lobules frequently develop in areas of RMD, suggesting progression of a single underlying disease process.

Review of en-face choroidal imaging using spectral-domain optical coherence tomography.

Investigations of choroidal vasculature have been of particular interest given choroidal vascular dysfunction are thought to be related with a number pathologic conditions such as central serous chorioretinopathy and various forms of AMD, including polypoidal choroidal vasculopathy. On the other hand, en face imaging of the choroid allows an exceptional alternative to histopathologic evaluation of the choroid, and can be used to quantify choroidal vascular structures. Our former study verified differences in the macular choroid in AMD and control patients previously noted on histopathologic studies. The use of phase-resolved approaches in larger population longitudinal studies reveal the sequence of RPE and choroidal changes in the pathogenesis of various AMD subtypes, which cannot be done using histopathology. Issues with lateral resolution of the OCT system in measuring choriocapillaris size could be solved by incorporating the axial dimension of the choriocapillaris into choriocapilaris diameter assessment (assuming the choriocapillaris are round in vivo), and by correcting for anisometric pixel resolution. Forthcoming studies are required to determine whether areas of choriocapillaris correlate with areas of RPD lesions.

A pilot study of morphometric analysis of choroidal vasculature in vivo, using en face optical coherence tomography.

PURPOSE: To study the ability of volumetric spectral domain optical coherence tomography (SD-OCT) to perform quantitative measurement of the choroidal vasculature in vivo. METHODS: Choroidal vascular density and vessel size were quantified using en face choroidal scans from various depths below the retinal pigment epithelium (RPE) in 58 eyes of 58 patients with either epiretinal membranes (ERM), early age-related macular degeneration (AMD), or reticular pseudo-drusen (RPD). For each patient, we used the macular volume scan (6×6 mm cube) for vessel quantification, while high-definition (HD) cross-section raster scans were used to qualitatively assess vascularity of the choroidal sub-layers, and measure choroidal thickness. RESULTS: Of the 58 patients, more were female (66% versus 34% male), of whom 14 (24%) had ERM, 11 (19%) early AMD, and 33 (57%) RPD. Compared to intact choriocapillaris in all ERM (100%), none of the RPD and only 5/11 (45%) early AMD eyes had visible choriocapillaris on either cross section or C-scans (p-value<0.001). When comparing select regions from the most superficial C-scans, early AMD group had lowest vascular density and RPD had highest (p-value 0.04). Qualitative evaluation of C-scans from all three groups revealed a more granular appearance of the choriocapillaris in ERM versus increased stroma and larger vessels in the RPD eyes. CONCLUSIONS: SD-OCT can be used to qualitatively and quantitatively assess choroidal vascularity in vivo. Our findings correlate to previously reported histopathologic studies. Lack of choriocapillaris on HD cross-sections or C-scans in all RPD and about half of early AMD eyes suggests earlier choroidal involvement in AMD and specifically, RPD.

Complement factor H 402H variant and reticular macular disease.

OBJECTIVE: To determine the association of high-risk alleles in the complement factor H (CFH; Y402H, rs1061170) and age-related maculopathy susceptibility (ARMS2; A69S, rs10490924) genes with reticular macular disease (RMD), a major clinical subphenotype of age-related macular degeneration (AMD). METHODS: Using retinal images from the Columbia Macular Genetics Study, we identified 67 subject individuals with RMD. A comparison group of 64 subjects with AMD without RMD was matched by ethnicity, age, sex, and AMD clinical stage. RESULTS: In the RMD group, 53 of 67 subjects (79.1%) were female, the mean age was 83 years, and 47 of 67 (70.1%) had late AMD, with closely matched values in the non-RMD group. The frequencies of the CFH 402H allele were 39.6% in the RMD group (53 of 134 individuals) and 58.6% in the non-RMD group (75 of 128 individuals) (χ(2) = 8.8; P = .003; odds ratio, 0.46 [95% confidence interval, 0.28-0.76]). The corresponding frequencies of the risk allele for ARMS2 were 44.0% (40 of 128 individuals) and 31.3% (40 of 128 individuals), respectively (χ(2) = 4.0; P = .045; odds ratio, 1.73 [95% confidence interval, 1.04-2.90]). Homozygosity for 402H was particularly associated with the absence of RMD, occurring in 8 of 67 subjects (11.9%) with RMD vs 24 of 64 subjects (37.5%) without RMD (P < .001). Retinal macular disease also was associated with hypertension among male patients. CONCLUSIONS: The AMD-associated CFH 402H risk variant is significantly associated with the absence of RMD but enhanced risk for RMD is conferred by the ARMS2 69S AMD risk allele. These results are consistent with the hypothesis that 402H may confer a survival benefit against certain infections, some of which may cause RMD. CLINICAL RELEVANCE: Reticular macular disease may be genetically distinct from the rest of AMD.

Image registration and multimodal imaging of reticular pseudodrusen.

PURPOSE: To characterize reticular pseudodrusen (RPD) by using a point-to-point comparison of the reticular pattern on infrared reflectance (IR), autofluorescence (AF), and red-free (RF) images registered with en face sections of the choroid from spectral domain optical coherence tomography (SD-OCT) scans. METHODS: A cross-sectional, retrospective study of all patients with the diagnosis of AMD who presented to the Doheny Retina Institute between December 2007 and November 2009 was conducted to identify patients with RPD. IR, AF, and RF images were obtained using confocal scanning laser ophthalmoscopy and were manually registered to OCT choroidal sections to study the location of RPD. The main outcome measured was point-to-point localization of RPD across multiple imaging modalities. RESULTS: Of the 153 patients with AMD, 51 had RPD. In all 51 patients (97 eyes), RPD appeared as areas of hypoautofluorescence and hyporeflectance on AF and IR imaging, respectively, and as hyporeflective interlacing networks on RF. Reticular lesions on AF, IR, and RF images consistently colocalized with stromal regions between large choroidal vessels on registered en face choroidal sections. In contrast, outer retinal changes and subretinal deposits tended to localize immediately adjacent to the RPD. CONCLUSIONS: Point-to-point correlation of registered IR, AF, and RF images consistently localizes the reticular pattern to the intervascular choroidal stroma on en face OCT sections. In contrast, subretinal deposits and disturbances of the inner outer segment on OCT did not colocalize with the RPD, and may represent secondary mechanical or biologic disturbances in the overlying RPE and outer retina.

Imaging characteristics of dry age-related macular degeneration.

PURPOSE: To review the current literature regarding the imaging characteristics of dry age-related macular degeneration (AMD) lesions, with a special focus on drusen and geographic atrophy imaging. We also explore the role of novel approach of hyperspectral imaging in AMD. METHODS: Review of current literature as well as findings in a small group of patients imaged with hyperspectral imaging. RESULTS: The use of optical coherence tomography, and especially fourier-domain devices, has enhanced our ability to classify various lesions of dry AMD. The increasing role of autofluorescence in characterization and prognostication in geographic atrophy is reviewed. The advances made in automated detection and multimodal imaging are highlighted, with their potential to revolutionize this area of research. CONCLUSIONS: Recent advances in retinal imaging have improved our understanding of the characteristics and prognostication of dry AMD, with an increasing role for multimodal imaging and image correlations. The potential future role of hyperspectral imaging in dry AMD is also presented herein.

A prospective study of reticular macular disease.

PURPOSE: To determine the risk of progression to advanced age-related macular degeneration (AMD) conferred by reticular pseudodrusen (RPD), an imaging presentation of reticular macular disease (RMD), in high-risk fellow eyes of subjects with AMD and unilateral choroidal neovascularization (CNV) in a large, prospective study. DESIGN: Cohort study. PARTICIPANTS: Two hundred seventy-one subjects with AMD; 94 with RPD and 177 without RPD. METHODS: Images from a cohort of 271 subjects with AMD in the Nutritional AMD treatment phase II (NAT 2) Study, a 3-year prospective study of subjects with unilateral CNV and large soft drusen in the fellow eye, were studied. The fellow eye, at high risk for advanced AMD developing, was the study eye. There were 5 visits per subject. Imaging at each visit consisted of color, red-free, and blue-light photography and fluorescein angiography. The images were analyzed for the presence of RPD, following disease progression throughout the 3-year study. MAIN OUTCOME MEASURES: The development of advanced AMD (CNV or geographic atrophy). RESULTS: For the 271 subjects who completed the full 3-year study, there was a significantly higher rate of advanced AMD (56% or 53/94) in fellow eyes with RPD at any visit compared with eyes without RPD (32% or 56/177; P < 0.0001, chi-square test; relative risk [RR], 1.8; 95% confidence interval [CI], 1.4-2.4). The chance of developing advanced AMD in the fellow eye in women with RPD (66%) was more than double that of women without RPD (30%; P < 0.00001; RR, 2.2; 95% CI, 1.6-3.1). CONCLUSIONS: To the authors' knowledge, this is the first comprehensive prospective study of RMD, a distinct clinical phenotype of AMD that includes RPD. It provides strong confirmation that RMD, a disease entity with stereotypical presentations across imaging methods, is associated with a high risk of progression to advanced AMD, perhaps on an inflammatory or vascular basis. Reticular macular disease deserves wider recognition and consideration by clinicians caring for patients with AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.