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Giant cell arteritis (GCA) is the most common vasculitis in adults and is associated with significant morbidity and mortality. Temporal artery biopsy (TAB) remains the gold standard for diagnosis in the United States; however, practices vary in the length of artery obtained and whether bilateral simultaneous biopsies are obtained.Retrospective chart review of all TABs performed at the Johns Hopkins Wilmer Eye Institute between July 1, 2007, and September 30, 2017.Five hundred eighty-six patients underwent TAB to evaluate for GCA. Of 404 unilateral biopsies, 68 (16.8%) were positive. Of 182 patients with bilateral biopsies, 25 (13.7%) had biopsies that were positive and 5 patients (2.7%) had biopsies that were discordant, meaning only 1 side was positive. There was no significant difference in the average postfixation length of positive and negative TAB specimens (positive mean length 1.38 ± 0.61 cm, negative mean length 1.39 ± 0.62 cm, P = 0.9).There is no significant association between greater length of biopsy and a positive TAB result in our data. Although the rate of positive results was not higher in the bilateral group compared with the unilateral group, 2.7% of bilateral biopsies were discordant, similar to previously published rates. Overall, this suggests that initial bilateral biopsy may increase diagnostic yield, albeit by a small amount.

Orbital lipolysis typically develops in the setting of a chronic catabolic state. The acute development and rapid progression of orbital lipolysis are much less commonly described. In this report, we present a rare case of a 64-year-old male who progressed from normal orbital fat content to marked orbital lipolysis in less than one month following episodes of undifferentiated shock, colonic perforation, and total colectomy. We outline the clinical course, describe the characteristic imaging findings, and provide a review of the cellular mechanisms underlying lipolysis. Our case suggests that multiple concurrent illnesses can combine to produce an extreme metabolic demand that may contribute to the uncommon development of rapidly-progressing orbital lipolysis.

Dedicated post-operative radiological evaluation following ophthalmologic procedures is relatively uncommon. However, given the ever-growing ophthalmologic procedural advancements and the increasing utilization of neuroimaging for myriad indications, the orbits are often imaged incidentally in a delayed post-procedural state. Regardless of the clinical scenario, it is important for neuroradiologists and other specialists commonly exposed to orbital imaging to be aware of both expected and abnormal post-operative imaging findings because misinterpreted normal features or unrecognized complications can result in vision-threatening delays in treatment or mismanagement. In this review article, we discuss many common ophthalmologic procedures, their indications, and most likely complications. We also provide illustrative operative photographs and radiological imaging examples. By understanding the surgical intent, recognizing the devices that are commonly used, and developing familiarity with the appearance of post-operative complications, pitfalls in interpretation can be avoided and patient outcomes ultimately improved.

Objective: We evaluated the safety and efficacy of an augmented BroadBand Light (BBL™) protocol on the upper and lower eyelids in improving meibomian gland dysfunction (MGD) and/or dry eye disease ...

Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting the medium and large-size arteries, and may present with a range of ophthalmic findings. This review will cover GCA epidemiology, pathophysiology, clinical presentation, diagnostic workup, and treatment.Epidemiology and PathophysiologyGCA is commonly found in elderly patients and individuals of Scandinavian descent. Recent publications suggest it may be more common in African Americans and Hispanics than previously thought. It is very rare in Asian and Middle-Eastern populations, and there is little data regarding African populations. Genetic studies have identified increased risk associated with HLA-DRB1*04. Rather than a response to a specific antigen such as varicella zoster virus, current immunology research suggests that GCA results from changes associated with the aging immune system.Clinical presentation to OphthalmologyArteritic anterior ischemic optic neuropathy is the most common ophthalmic manifestation of GCA, but central or branch retinal artery occlusion, ophthalmic artery occlusion, cranial neuropathies causing diplopia, and more rarely anterior segment ischemia and anisocoria may also occur. Clinical testing including visual field testing, OCT, OCT-A, ICG and fluorescein angiography can be helpful in suggesting a diagnosis in addition to the clinical exam.Diagnostic WorkupGCA is ultimately a clinical diagnosis, but it is usually supported with lab results, pathology, and/or imaging. Temporal artery biopsy (TAB) remains the gold standard diagnostic test although its sensitivity is debated and practice patterns still vary with respect to sample length and whether unilateral or simultaneous bilateral biopsies are performed. Some studies have reported higher sensitivity of ultrasounds over TAB, with added benefits of time efficiency and cost effectiveness, promoting the diagnostic use of ultrasounds. MRI and even PET CT protocols offer additional options for less invasive diagnostic testing.TreatmentVision-threatening GCA is treated acutely with emergent admission for intravenous methylprednisolone, and long-term high dose oral corticosteroids remain the standard of care, despite common and sometimes serious side effects. The use of steroid-sparing alternatives such as tocilizumab is becoming more common and additional agents are being investigated.

Recent survey studies have demonstrated wide variability in practice patterns regarding the management of antithrombotic medications in oculofacial plastic surgery. Current evidence and consensus guidelines are reviewed to guide perioperative management of antithrombotic medications.Comprehensive literature review of PubMed database on perioperative use of antithrombotic medication.Perioperative antithrombotic management is largely guided by retrospective studies, consensus recommendations, and trials in other surgical fields due to the limited number of studies in oculoplastic surgery. This review summarizes evidence-based recommendations from related medical specialties and provides context for surgeons to tailor antithrombotic medication management based on patient's individual risk. The decision to continue or cease antithrombotic medications prior to surgery requires a careful understanding of risk: risk of intraoperative or postoperative bleeding versus risk of a perioperative thromboembolic event. Cessation and resumption of antithrombotic medications after surgery should always be individualized based on the patient's thrombotic risk, surgical and postoperative risk of bleeding, and the particular drugs involved, in conjunction with the prescribing doctors. In general, we recommend that high thromboembolic risk patients undergoing high bleeding risk procedures (orbital or lacrimal surgery) may stop antiplatelet agents, direct oral anticoagulants, and warfarin including bridging warfarin with low-molecular weight heparin. Low-risk patients, regardless of type of procedure performed, may stop all agents. Decision on perioperative management of antithrombotic medications should be made in conjunction with patient's internist, cardiologist, hematologist, or other involved physicians which may limit the role of guidelines depending on patient risk and should be used on a case-by-case basis. Further studies are needed to provide oculofacial-specific evidence-based guidelines.

An isolated defect in the lateral orbital wall is an uncommon occurrence, although cases of orbital floor, roof, and medial wall spontaneous dehiscence have been described in the literature. Here, we describe a lateral orbital wall defect in a patient with thyroid eye disease - which may be related to bony remodeling or may represent a rare congenital anomaly. Computed tomography (CT) prior to decompression surgery revealed a defect in the left lateral orbital wall. At the time of orbital decompression, prolapse of buccal fat into the orbit was noted once the subperiosteal plane was entered along the lateral orbital wall in the area of this bony defect. Literature review revealed only a few previous reports of lateral wall abnormalities, including two involving the inferior orbital fissure; one other case was associated with Down syndrome, and other reports consist of sphenoid hypoplasia associated with neurofibromatosis.

Purpose: Thermal injury to the optic nerve is a potential complication of bony decompression of the orbital apex. An animal model was used to compare and contrast temperature change while removing ...

Purpose: This study describes the clinical features and management of epiblepharon as a manifestation of thyroid eye disease (TED). In addition, we compare the frequency and age in Asian and non-Asian patients, and discuss pathophysiologic implications. Design: Retrospective case-control study. Methods: This is a single-center retrospective review that identified 172 adult patients (age 19 to 83) with TED that were consecutively evaluated by 1 author (T.J.M.) between December 2015 and July 2018. Diagnosis of TED and epiblepharon was based upon clinical assessment as documented in the medical record. Results: In a cohort of 172 patients (mean age 52; 138 female), 3 patients with acquired epiblepharon were identified, all of whom were Asian. The proportion of affected Asian patients (3/of 17, 17.6%) was significantly higher than that of non-Asian patients (0/155, P

Melanomas of the conjunctiva and eyelid present unique management challenges for the ophthalmologist and ocular oncologist. Surgical excision, a mainstay of treatment, may be disfiguring with variable rates of local recurrence.1 Conjunctival melanomas have a local recurrence rate ranging from 18% to 83% with data largely coming from patients treated with excision with or without cryotherapy.2–4 Cutaneous melanomas of the eyelid skin have a local recurrence rate ranging from 7% to 78% depending on technique and extent of excision.5–7 The rate of regional lymph node metastasis was 41% in a study of conjunctival melanoma patients treated primarily with local excision, the authors compared their finding to rates in cutaneous melanoma of the head and neck which ranged from 14% to 44% or eyelid skin melanoma at 29%.4 Efforts to improve outcomes of these tumors have continually advanced with surgical techniques and adjunctive treatments such as topical therapy, radiation, and systemic chemotherapy.8 Recent advances in immunotherapy, specifically checkpoint inhibitors, has allowed for primary and adjuvant treatment of cutaneous melanomas with medical therapy. These have been successful in the setting of metastatic cutaneous melanoma and other cancers. This review of the literature summarizes the current understanding and use of checkpoint inhibitors, with a particular focus for the ophthalmic surgeon. Immune checkpoint inhibitors are relatively new therapies, developed with the rationale of stimulating a patient’s own immune system to better respond to malignancies. This strategy progressed from the discovery of specific receptor proteins that promote immune tolerance, that is, inhibit immune responsiveness, which tumors may take advantage of to proliferate unhindered. Monoclonal antibodies were developed to block these cellular checkpoints. Clinically available therapies include ipilimumab, which targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), nivolumab, pembrolizumab, and cemiplimab, which target programmed cell death-1 (PD-1), and atezolizumab, avelumab, and durvalumab, which target programmed cell death ligand-1 (PD-L1). Checkpoint inhibitors have demonstrated efficacy in a range of malignancies including non–small cell lung cancer, urothelial cancer, renal cell cancer, squamous cell carcinoma of the head and neck, Merkel cell carcinoma, and metastatic cutaneous melanoma.9 In recent years there has been emerging interest in checkpoint inhibitor therapy for oculoplastic applications, specifically eyelid and conjunctival melanomas.10 However, there is limited clinical experience with the use of these drugs for this indication. Eyelid and conjunctival melanomas were not specifically studied in the trials leading to the development of these therapies, resulting in limited knowledge of their potential benefits and risks. This chapter reviews the available literature regarding checkpoint inhibitors for eyelid and conjunctival melanomas.

Suction aspiration, which has not yet been described in the treatment for myiasis in the periorbital and facial regions, was used to achieve rapid resolution of maggot burden in a 78-year-old patient who presented with a large ulcerated squamous cell carcinoma of the face. This technique also facilitates submission of parasite samples for further analysis. Suction aspiration had no complications, such as significant residual ruptured maggots in the wound or eye injury. Suction aspiration is a safe and efficient technique to reduce maggot burden that has advantages over classic myiasis treatments, especially near the eyes and airway.

We investigate lying behavior when lying is undetectable and payoffs are split with charity. 524 Participants are randomly assigned to share all, some, or none of the payoff with a charity of their choice. The payoff earned depends on the number participants report after rolling a die in private (i.e., there are clear incentives to lie). This allows us to examine lying behavior as the share of the payoffs to charity gradually increases. Our results are as follows: (i) participants in all groups lie to inflate their number; (ii) lying decreases drastically when the charity is the sole recipient; and (iii) post-experiment surveys reveal that those participants who are most likely to have lied are the least likely to admit it. Finally, our data suggests that lying is not correlated with any observable sociodemographic characteristic.

Cosmetic injection of hyaluronic acid (HA) and other fillers is increasingly common, and the late complications of these relatively new procedures are now coming to medical attention. Three patients with delayed periocular swelling that began years after injection of HA are described, with CT, MRI, and histopathologic characterization. While HA fillers are marketed as having a temporary effect of several months, the authors demonstrate that they may persist in the body for up to 9 years. Unlike most previous reports, there was no inflammatory reaction or encapsulation, simply infiltration into more superficial subcutaneous layers. All cases improved after surgical biopsy and hyaluronidase injections. Delayed periocular swelling after filler injections from several years prior can mimic serious medical conditions. With a detailed history and high index of suspicion, one may avoid a costly and invasive workup.

Orbital invasion of pituitary adenomas has been previously reported. In this report, the authors describe a 71-year-old female with a prolactinoma that presented with invasion of and apoplexy within the orbit. The patient underwent exenteration, followed by rapid tumor recurrence and growth. Given the hemorrhagic nature of the tumor, she subsequently underwent preoperative embolization and surgical resection. This case is notable in that it illustrates both apoplexy of a pituitary tumor within the orbit and the benefit of presurgical embolization.

In this article we review bony changes resulting from alterations in intracranial pressure (ICP) and the implications for ophthalmologists and the patients for whom we care. Before addressing ophthalmic implications, we will begin with a brief overview of bone remodeling. Bony changes seen with chronic intracranial hypotension and hypertension will be discussed. The primary objective of this review was to bring attention to bony changes seen with chronic intracranial hypotension. Intracranial hypotension skull remodeling can result in enophthalmos. In advanced disease enophthalmos develops to a degree that is truly disfiguring. The most common finding for which subjects are referred is ocular surface disease, related to loss of contact between the eyelids and the cornea. Other abnormalities seen include abnormal ocular motility and optic atrophy. Recognition of such changes is important to allow for diagnosis and treatment prior to advanced clinical deterioration. Routine radiographic assessment of bony changes may allow for the identification of patient with abnormal ICP prior to the development of clinically significant disease.

A 62-year-old man developed bilateral blurred vision associated with bilateral optic disc swelling shortly after receiving his third dose of the tumor necrosis factor-alpha (TNF-α) inhibitor golimumab, that he took for psoriatic arthritis. An extensive assessment including magnetic resonance imaging, lumbar puncture, and serologies was negative. He was treated with systemic corticosteroids and the golimumab was stopped, after which his vision improved and his disc swelling resolved. We postulate that the bilateral, simultaneous anterior optic neuropathies in this patient were due to golimumab, representing a rare but well-documented serious adverse event associated with TNF-α inhibitors.

While scuba diving, the left medial canthus of a 53-year-old man was pierced by a needlefish. He immediately lost vision in his left eye. An orbital computed tomographic scan showed the needlefish jaw in the left optic canal. The left medial orbit was explored surgically but no foreign object was removed. One month later, MRI confirmed the presence of the retained needlefish jaw. A conservative approach was taken and the patient remained stable over 3 months of follow-up.

Brown syndrome is characterised by impaired supraduction worse in adduction due to a restricted superior oblique tendon passing through the trochlea. A few reports have previously described Brown syndrome after upper eyelid surgery, including blepharoplasty and ptosis repair. The authors describe two additional cases of Brown syndrome following ptosis repair. The first case is a 65-year-old woman with new-onset vertical binocular diplopia following bilateral levator advancement surgery. Ocular motility examination demonstrated moderate impairment of elevation in adduction. The second case is a 35-year-old woman who presented with new-onset intermittent binocular diplopia following right upper lid ptosis repair. Examination revealed large vertical fusional amplitudes and a large left intermittent hyperphoria in an alignment pattern consistent with Brown syndrome. Despite presenting after surgery, these cases differ in mechanism. The first case likely occurred due to intraoperative impairment of the superior oblique tendon sheath or trochlea, whereas the second case represented an unmasking of a long-standing, previous vertical strabismus that was consistent with a Brown syndrome pattern.

To evaluate the relative frequencies of arteritic and nonarteritic anterior ischemic optic neuropathy (AION) in an Arab population and to compare and contrast these findings with known epidemiological data from Caucasian populations.A retrospective review of the medical records of all patients diagnosed with AION at the King Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia, between 1997 and 2012.Of 171 patients with AION, 4 had biopsy-proven giant-cell arteritis (GCA). The relative frequencies of arteritic anterior ischemic optic neuropathy (AAION) and nonarteritic anterior ischemic optic neuropathy (NAION) in this Arab cohort were 2.3% and 97.7%, respectively.The relative frequencies of arteritic anterior ischemic optic neuropathy and nonarteritic anterior ischemic optic neuropathy differ between Arab and North American clinic-based populations, with giant-cell arteritis-related ischemia being much less frequent in Saudi Arabia.

Many abnormalities of the orbit present with neuro-ophthalmic findings, such as impaired ocular motility or alignment, and sensory changes, including optic neuropathy. Comprehensive coverage of all orbital diseases is beyond the scope of this article. This review focuses on diagnosis and management of the most common and the most vision- or life-threatening orbital conditions as well as more recently discovered entities and points of active controversy. These conditions include orbital trauma, vascular disease, inflammatory and infectious diseases, and neoplasms. Common presenting symptoms and associated neuro-orbital diseases also are summarized.

Importance Giant cell arteritis (GCA) is the most common vasculitis in adults and is associated with significant morbidity and mortality. Its incidence has been carefully studied in white populations, yet its relevance among other racial and ethnic groups is less well known. Objective To examine the incidence of biopsy-proven GCA (BP-GCA) in a tertiary care center–based population with a sizeable proportion of black patients. Design, Setting, and Participants This retrospective cohort study identified all patients who underwent temporal artery biopsy (TAB) from July 1, 2007, through September 30, 2017, using the electronic medical record system at the Johns Hopkins Wilmer Eye Institute. Associations between self-reported race, sex, and age were explored and compared with all other patients attending the hospital over the same period. Data were analyzed from November 1, 2017, through July 31, 2018. Main Outcomes and Measures Estimated incidence rates of BP-GCA in black and white patients. Results Among 586 patients who underwent TAB (mean [SD] age, 70.5 [11.1] years; age range, 32-103 years; 423 [72.2%] women), 167 (28.5%) were black, 382 (65.2%) were white, and 37 (6.3%) were other or unknown. Of 573 individuals 50 years and older, 92 (16.1%) had BP-GCA; 14 were black (8.4% of all black patients undergoing testing) and 75 were white (19.6% of all white patients undergoing testing). Crude annual incidence rates for BP-GCA were 2.9 (95% CI, 1.3-5.5) per 100 000 for black and 4.2 (95% CI, 3.0-5.6) per 100 000 for white patients within the study population. Population-adjusted age- and sex-standardized incidence rates were 3.1 (95% CI, 1.0-5.2) and 3.6 (95% CI, 2.5-4.7) per 100 000 for black and white patients, respectively (difference, 0.5; 95% CI, −1.7 to 2.7;P = .70). The incidence rate ratio was 1.9 in women compared with men (95% CI, 1.1-3.4;P = .03) but was not significant in white compared with black patients (1.2; 95% CI, 0.6-2.4;P = .66). Conclusions and Relevance In our cohort, BP-GCA occurred more commonly in women, but rates were similar between races. These findings do not appear to support the conclusion that GCA occurs more frequently in white compared with black patients.

A 79-year-old man presented to the ophthalmology clinic with acute-onset left orbital and periorbital swelling, 6 days following surgery to revise a zygomatic implant to anchor his dentures. On evaluation, there was left eye proptosis with ipsilateral facial crepitus. Emphysema was confirmed on computed tomography. With visual function and motility remaining intact, he was observed without intervention. Within 2 weeks, his evaluation returned to baseline. Periorbital emphysema is a rare complication of dental procedures. Awareness of this potential complication enables timely diagnosis and avoidance of unnecessary therapy.

Objective To investigate potential risk factors associated with incident nuclear, cortical, and posterior subcapsular (PSC) cataracts and cataract surgery in participants in the Age-Related Eye Disease Study (AREDS). Design Clinic-based prospective cohort study. Participants Persons (n = 4425) 55 to 80 years of age enrolled in a controlled clinical trial of antioxidant vitamins and minerals, AREDS, for age-related macular degeneration and cataract. Methods Lens photographs were graded centrally for nuclear, cortical, and PSC opacities using the AREDS system for classifying cataracts. Type-specific incident cataracts were defined as an increase in cataract grade from none or mild at baseline to a grade of moderate at follow-up, also with a grade of at least moderate at the final visit, or cataract surgery. Cox regression analyses were used to assess baseline risk factors associated with type-specific opacities and cataract surgery. Main Outcome Measures Moderate cataract was defined as a grade of 4.0 or more for nuclear opacity, 10% or more involvement within the full visible lens for cortical opacity, and 5% or more involvement of the central 5-mm circle of the lens for PSC opacity. These were graded on baseline and annual lens photographs. Results A clinic-based cohort of 4425 persons 55 to 80 years of age at baseline was followed up for an average of 9.8±2.4 years. The following associations were found: increasing age with increased risk of all types of cataract and cataract surgery; males with increased risk of PSC and decreased risk of cortical cataracts; nonwhite persons with increased risk of cortical cataract; hyperopia with decreased risk of PSC, nuclear cataract, and cataract surgery; Centrum (Wyeth Consumer Healthcare, Madison, NJ) use with decreased risk of nuclear cataract; diabetes with increased risk of cortical, PSC cataract, and cataract surgery; higher educational level with decreased risk of cortical cataract; and smoking with increased risk of cortical cataract and cataract surgery. Estrogen replacement therapy in female participants increased the risk of cataract surgery. Conclusions These findings largely are consistent with the results of previous studies, providing further evidence for possible modifiable risk factors for age-related cataract. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Our understanding of the potential role intracranial pressure (ICP) may play in the pathophysiology of glaucoma is evolving. ICP can have a profound effect on the optic nerve; edema of the optic disc is an accepted consequence of elevation in ICP, and optic disc blood flow is known to be affected by ICP. Deformation of the orbit also is a known consequence of aberrations in ICP. Therefore, it is plausible that local alterations in optic nerve structure, blood supply, or axonal transport could result from changes in ICP. This article will summarize the relationship between ICP and the eye, specifically focusing on hypothesized relationships between ICP and glaucoma and the current evidence supporting or refuting ICP as a risk factor for glaucoma.

PURPOSE. Peripheral eye length (PEL) provides a measure of overall eye shape, which may play a role in the development of myopia. The current study explores the distribution and heritability of PEL, relative PEL (RPEL, defined as PEL minus axial eye length) and relative ratio PEL (RRPEL, defined as PEL divided by axial eye length) in Chinese children and adolescents. METHODS. Subjects included both male and female youths participating in the Guangzhou Twin Eye Study. Eye length was measured by partial coherence laser interferometry axially, 408 temporally (PEL-T40) and 408 nasally (PEL-N40). Structural equation modeling (SEM) was used to estimate the relative contribution of genetic and environmental factors on PEL, RPEL, and RRPEL, adjusting for age and sex. RESULTS. We examined 104 monozygotic (MZ) and 54 dizygotic (DZ) twins aged 8 to 20 years old. The intraclass correlation coefficients were 0.89 for PEL-T40, 0.92 for PEL-N40, 0.80 for RPEL-T40, 0.73 for RPEL-N40, 0.77 for RRPEL-T40, and 0.73 for RRPEL-N40 in MZ pairs, and 0.52, 0.50, 0.39, 0.58, 0.37, and 0.58 in DZ pairs, respectively. The best fit adjusted models estimated that additive genetic effects accounted for approximately 86.2%, 89.8%, 79.9%, 75.5%, 77.1%, and 74.5% of the variance for the above mentioned traits, respectively, while dominant genetic effects and shared environmental factors were negligible. CONCLUSIONS. Additive genetic effects had a substantial influence on phenotypic variation in PEL and RPEL, suggesting genetic rather than environmental factors play a major role in determining eye shape. (Invest Ophthalmol Vis Sci. 2013; 54:1048‐1053) DOI:10.1167/iovs.12-10066

To investigate potential risk factors associated with incident nuclear, cortical, and posterior subcapsular (PSC) cataracts and cataract surgery in participants in the Age-Related Eye Disease Study (AREDS).Clinic-based prospective cohort study.Persons (n = 4425) 55 to 80 years of age enrolled in a controlled clinical trial of antioxidant vitamins and minerals, AREDS, for age-related macular degeneration and cataract.Lens photographs were graded centrally for nuclear, cortical, and PSC opacities using the AREDS system for classifying cataracts. Type-specific incident cataracts were defined as an increase in cataract grade from none or mild at baseline to a grade of moderate at follow-up, also with a grade of at least moderate at the final visit, or cataract surgery. Cox regression analyses were used to assess baseline risk factors associated with type-specific opacities and cataract surgery.Moderate cataract was defined as a grade of 4.0 or more for nuclear opacity, 10% or more involvement within the full visible lens for cortical opacity, and 5% or more involvement of the central 5-mm circle of the lens for PSC opacity. These were graded on baseline and annual lens photographs.A clinic-based cohort of 4425 persons 55 to 80 years of age at baseline was followed up for an average of 9.8±2.4 years. The following associations were found: increasing age with increased risk of all types of cataract and cataract surgery; males with increased risk of PSC and decreased risk of cortical cataracts; nonwhite persons with increased risk of cortical cataract; hyperopia with decreased risk of PSC, nuclear cataract, and cataract surgery; Centrum (Wyeth Consumer Healthcare, Madison, NJ) use with decreased risk of nuclear cataract; diabetes with increased risk of cortical, PSC cataract, and cataract surgery; higher educational level with decreased risk of cortical cataract; and smoking with increased risk of cortical cataract and cataract surgery. Estrogen replacement therapy in female participants increased the risk of cataract surgery.These findings largely are consistent with the results of previous studies, providing further evidence for possible modifiable risk factors for age-related cataract.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background Advanced age contributes to clinical manifestations of many retinopathies and represents a major risk factor for age-related macular degeneration, a leading cause of visual impairment and blindness in the elderly. Rod photoreceptors are especially vulnerable to genetic defects and changes in microenvironment, and are among the first neurons to die in normal aging and in many retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptor vulnerability and potential biomarkers of the aging process in this highly specialized cell type are unknown. Methodology/Principal Findings To discover aging-associated adaptations that may influence rod function, we have generated gene expression profiles of purified rod photoreceptors from mouse retina at young adult to early stages of aging (1.5, 5, and 12 month old mice). We identified 375 genes that showed differential expression in rods from 5 and 12 month old mouse retina compared to that of 1.5 month old retina. Quantitative RT-PCR experiments validated expression change for a majority of the 25 genes that were examined. Macroanalysis of differentially expressed genes using gene class testing and protein interaction networks revealed overrepresentation of cellular pathways that are potentially photoreceptor-specific (angiogenesis and lipid/retinoid metabolism), in addition to age-related pathways previously described in several tissue types (oxidative phosphorylation, stress and immune response). Conclusions/Significance Our study suggests a progressive shift in cellular homeostasis that may underlie aging-associated functional decline in rod photoreceptors and contribute to a more permissive state for pathological processes involved in retinal diseases.

Nicotine administration potentiates conditioned reinforcement in rats, an effect that persists for weeks after chronic exposure. Little is known regarding the nicotinic receptor subtypes that may mediate this effect.The purpose of this study was to determine whether beta2-subunit-containing nicotinic acetylcholine receptors (beta2*nAChRs) are necessary for lasting effects of nicotine on conditioned and primary reinforcement in mice.Beta2 knockout (beta2KO) and wild-type (WT) mice received 14 days of nicotine exposure (NIC, 200 microg/ml in 2% saccharin) or saccharin alone (SAC) in their drinking water. Five days later, mice received paired presentations of a conditioned stimulus (CS) with water unconditioned stimulus (US) or explicitly unpaired presentations of the CS and US during Pavlovian discriminative approach training. Training was followed by two conditioned reinforcement tests. Mice were subsequently tested for food-reinforced responding in the absence of explicit cues followed by a progressive ratio test.During conditioned reinforcement testing, only mice in the paired condition showed increased responding in the CS-reinforced aperture over inactive apertures. WT-NIC mice showed enhanced conditioned reinforcement compared to WT-SAC animals. beta2KO-SAC mice showed elevated conditioned reinforcement compared to WT-SAC subjects, but beta2KO-NIC and beta2KO-SAC mice did not differ in responding with conditioned reinforcement. Prior nicotine exposure did not alter food-reinforced responding but resulted in elevated break points for food in both genotypes.These data show that nicotine exposure enhances conditioned reinforcement in mice and indicate that beta2*nAChRs are necessary for nicotine-dependent enhancement of incentive aspects of motivation but not motivation for primary reinforcement measured by progressive ratio responding.

Indirect traumatic optic neuropathy (ITON) refers to optic nerve injury resulting from impact remote to the optic nerve. The mechanism of injury is not understood, and there are no confirmed protocols for prevention, mitigation or treatment. Most data concerning this condition comes from case series of civilian patients suffering blunt injury, such as from sports- or motor vehicle-related concussion, rather than military-related ballistic or blast damage. Research in this field will likely require the development of robust databases to identify patients with ITON and follow related outcomes, in addition to both in-vivo animal and virtual human models to study the mechanisms of damage and potential therapies.