Angiographic Features of Iris Melanocytic Tumors: Nevus versus Melanoma.

Introduction: Determining the nature of iris melanocytic tumors based on clinical exam alone remains challenging. Tumor-associated vasculature of iris melanocytic lesions may facilitate the ability to discern between iris nevus and melanoma. Methods: In a single-institution, retrospective, observational study of 45 patients with pathologically confirmed iris melanoma and 15 patients with iris nevi that were either clinically stable or pathologically confirmed were included. Tumor characteristics and associated vasculature were identified on clinical exam and slit-lamp photographs. Fluorescein angiographic parameters including feeder vessels, intrinsic vessels, leakage, masking, and angiographic silence were assessed. Results: Feeder vessels were present in 17 (43%) melanomas and were absent in the nevus group (p = 0.002). Thirty-three (83%) iris melanomas and 5 (33%) iris nevi were observed to have intrinsic vessels, and a statistically significant association of intrinsic vessels with malignancy (p = 0.001) was noted. Fluorescein leakage was also observed more frequently in iris melanoma 39 (98%) than in nevi 9 (60) with a significant difference (p = 0.001). Angiographic silence occurred in 3 nevi (20%) and was not observed in any melanoma (p = 0.017). Overall, the presence of intrinsic vessels +/- feeder vessels had high sensitivity (0.85) and high positive predictive value (0.87) for diagnosis of iris melanoma. Conclusions: Anterior segment fluorescein angiography allows for the assessment of tumor-associated vascular patterns and demonstrates utility in differentiating iris nevi from melanoma. Feeder vessels were only observed in iris melanoma and were absent in iris nevi. The intrinsic vessels were present more frequently in melanomas and are thus associated with malignancy. Angiographic silence is indicative of iris nevi.

Dark-Without-Pressure Lesion in a Patient in Their Mid-40s.

This case report discusses a diagnosis of a dark-without-pressure lesion in an otherwise asymptomatic patient in their mid-40s.

INTRAVITREAL FLUOCINOLONE ACETONIDE IMPLANT FOR RADIATION RETINOPATHY: Report of Preliminary Findings.

PURPOSE: To assess the efficacy of a 0.18 mg intravitreal fluocinolone acetonide (FA) implant (Yutiq, EyePoint Pharmaceuticals, Watertown, MA) as a treatment option for patients with radiation retinopathy-related cystoid macular edema. METHODS: A retrospective review of seven patients treated for uveal melanoma who developed radiation retinopathy-related cystoid macular edema. They were initially treated with intravitreal anti-vascular endothelial growth factor and/or steroid injections and then transitioned to intravitreal FA implant. Primary outcomes include best-corrected visual acuity, central subfield thickness, and number of additional injections. RESULTS: After FA implant insertion, best-corrected visual acuity and central subfield thickness remained stable in all patients. The variance in best-corrected visual acuity decreased from 75.5 ETDRS letters (range 0-199 letters) to 29.8 (range 1.2-134) after FA implant insertion. Mean central subfield thickness was 384 µ m (range 165-641) and 354 µ m (range 282-493) before and after FA implant insertion, resulting in a 30- µ m mean reduction. The number of intravitreal injections (average 4.9, range 2-10) decreased after intravitreal FA implant insertion with only two patients requiring one additional FA implant (average 0.29, range 0-1) over a mean of 12.1 months (range 0.9-18.5) follow-up. CONCLUSION: Intravitreal FA implant is an effective treatment for cystoid macular edema radiation retinopathy. The slow release of steroid allows for sustained control of macular edema, which correlated with stable visual acuity and decreased injection burden for patients.

Anterior Uveal Melanocytoma: Role of Diagnostic FNAB.

Introduction: Anterior uveal melanocytoma (AUM) pose a diagnostic challenge as they can mimic growing melanomas. Establishing a definitive diagnosis of melanocytoma necessitates cytologic or histopathologic confirmation. We describe the clinical presentation and characteristics of fifteen pathologically proven AUM cases and assess the role of fine needle aspiration biopsy (FNAB) as a safe and effective tool for diagnosis. Methods: Retrospective review of pathologically confirmed AUM cases was performed. Demographic data, presenting symptoms, clinical features, diagnostic approach, cytological and histological features, and clinical outcomes were collected. Results: Fifteen patients with pathologically confirmed AUM were identified. The mean and median age of diagnosis were 50 and 53 years, respectively (range 3-77 years). The melanocytoma was localized to the iris (5, 33%) or ciliary body (7, 47%), and 3 patients had iridociliary involvement (20%). Presentation was due to concern for growth in 4 (29%), visual symptoms in 1 (7%), and was an incidental finding in 10 (64%) patients. Pigmentation of the tumor varied with 9 (60%) appearing brown and 3 (20%) black in color. The color of 3 (20%) ciliary body tumors could not be assessed. The diagnosis was confirmed with FNAB in 6 (40%), excisional biopsy in 7 (47%), and incisional biopsy in 2 (13%). Cytologic and histologic preparations demonstrated predominance of round to polygonal cells with heavily pigmented cytoplasm and small round nuclei. One patient who underwent excisional biopsy had prior FNAB that was interpreted as suspicious for melanoma (false-positive). Instances of false-negative cytology were not observed as demonstrated by the subsequent stable clinical course during the mean follow-up of 21.2 months (range = 1.0-63.0 months). FNAB-related complications were not observed in any case. Conclusion: FNAB offers a minimally invasive and safe diagnostic approach for pathologic confirmation of AUM. However, limitations of FNAB including false-negative and false-positive biopsies must be considered when excluding underlying malignancy. Continued observation to document tumor stability should be considered.

Oral minocycline for the treatment of retinitis pigmentosa-associated cystoid macular edema: results of a phase I/II clinical trial.

PURPOSE: The etiology of retinitis pigmentosa (RP)-associated cystoid macular edema (CME) has been related to retinal neuroinflammation and microglial activation. Minocycline, a drug FDA-approved for anti-microbial indications, also inhibits microglial activation and expression of inflammatory mediators. This study investigates the safety and efficacy of oral minocycline as primary treatment for RP-associated CME. METHODS: A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with RP-associated CME. Participants had lead-in assessments prior to the initiation of oral minocycline 100 mg twice daily for 12 months. Main outcome variables included changes in best-corrected visual acuity (BCVA) and retinal central subfield thickness (CST) measured using spectral domain optical coherence tomography relative to mean of pre-treatment measurements. RESULTS: The study drug was well tolerated and not associated with any severe adverse events. No significant changes in mean BCVA from study baseline were noted in either the study eye (+ 0.7 ± 4.1 letters at 6 months, - 1.1 ± 1.7 letters at 12 months) or the qualifying fellow eye (- 0.3 ± 3.4 letters at 6 months, - 0.3 ± 4.6 letters at 12 months) (p > 0.05 for all comparisons). Mean percentage changes in CST from baseline however decreased progressively with treatment (decreases at 6 and 12 months: study eyes 3.9 and 9.8%; qualifying fellow eyes 1.4 and 7.7%). Considering all eyes (n = 10), mean percentage CST decrease at 6 and 12 months was 2.7 ± 9.5% (p = 0.39) and 8.7 ± 9.5% (p = 0.02) respectively. CONCLUSION: Oral minocycline administration over 12 months was associated with no significant changes in mean BCVA and a small but progressive decrease in mean CST. TRIAL REGISTRATION: NCT02140164 (05/2014).

Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy: Demographics, Risk Factors, and Visual Outcomes.

BACKGROUND: Although nonarteritic anterior ischemic optic neuropathy is a well-known cause of vision loss, it typically presents unilaterally. Simultaneous, bilateral nonarteritic anterior ischemic optic neuropathy (sNAION) is rare and poorly studied in comparison. This study seeks to characterize the clinical features and risk factors of patients with sNAION compared with unilateral NAION (uNAION). METHODS: In this retrospective case-control study, we reviewed 76 eyes (38 patients) with sNAION and 38 eyes (38 patients) with uNAION (controls) from 4 academic institutions examined between 2009 and 2020. Demographic information, medical history, medication use, symptom course, paraclinical evaluation, and visual outcomes were collected for all patients. RESULTS: No significant differences were observed in demographics, comorbidities and their treatments, and medication usage between sNAION and uNAION patients. sNAION patients were more likely to undergo an investigative work-up with erythrocyte sedimentation rate measurement ( P = 0.0061), temporal artery biopsy ( P = 0.013), lumbar puncture ( P = 0.013), and MRI ( P < 0.0001). There were no significant differences between the 2 groups for visual acuity, mean visual field deviation, peripapillary retinal nerve fiber layer thickness, or ganglion cell-inner plexiform layer thickness at presentation, nor at final visit for those with ≥3 months of follow-up. The sNAION eyes with ≥3 months of follow-up had a smaller cup-to-disc ratio (CDR) at final visit ( P = 0.033). Ten patients presented with incipient NAION, of which 9 suffered vision loss by final visit. CONCLUSION: Aside from CDR differences, the risk factor profile and visual outcomes of sNAION patients seem similar to those of uNAION patients, suggesting similar pathophysiology.

Silicone oil tamponade in managing recalcitrant endophthalmitis after cataract surgery secondary to Clostridium intestinale.

A woman presented two weeks after uncomplicated cataract surgery with decreased visual acuity from endophthalmitis. One week after initial management with intravitreal antibiotics, her visual acuity decreased further, undergoing pars plana vitrectomy with intravitreal and intravenous antimicrobial coverage with preliminary improvement. Three days after vitrectomy, her vision decreased with recurrent inflammation. Initial cultures grew Clostridium intestinale She underwent repeat vitrectomy with silicone oil tamponade with no subsequent recurrence. The silicone oil was removed after 4 months and her visual acuity returned to 20/20 after 1 month and through 1 year of follow-up. Postoperative endophthalmitis is rare, with cases due to Clostridium species particularly destructive. In this first reported case of C. intestinale endophthalmitis, conventional management did not achieve lasting quiescence until silicone oil tamponade was employed. Pars plana vitrectomy with silicone oil tamponade should be considered in the management of recurrent endophthalmitis or endophthalmitis secondary to a recalcitrant microbe.

Circulating platelet aggregates damage endothelial cells in culture.

BACKGROUND: Presence of circulating endothelial cells (CECs) in systemic circulation may be an indicator of endothelial damage and/or denudation, and the body's response to repair and revascularization. Thus, we hypothesized that aggregated platelets (AgPlts) can disrupt/denude the endothelium and contribute to the presence of CEC and EC-derived particles (ECDP). METHODS: Endothelial cells were grown in glass tubes and tagged with/without 0.5 µm fluorescent beads. These glass tubes were connected to a mini-pump variable-flow system to study the effect of circulating AgPlts on the endothelium. ECs in glass tube were exposed to medium alone, nonaggregated platelets (NAgPlts), AgPlts, and 90 micron polystyrene beads at a flow rate of 20 mL/min for various intervals. Collected effluents were cultured for 72 h to analyze the growth potential of dislodged but intact ECs. Endothelial damage was assessed by real time polymerase chain reaction (RT-PCR) for inflammatory genes and Western blot analysis for von Willebrand factor. RESULTS AND CONCLUSION: No ECs and ECDP were observed in effluents collected after injecting medium alone and NAgPlts, whereas AgPlts and Polybeads drastically dislodged ECs, releasing ECs and ECDP in effluents as the time increased. Effluents collected when endothelial cell damage was seen showed increased presence of von Willebrand factor as compared to control effluents. Furthermore, we analyzed the presence of ECs and ECDPs in heart failure subjects, as well as animal plasma samples. Our study demonstrates that circulating AgPlts denude the endothelium and release ECs and ECDP. Direct mechanical disruption and shear stress caused by circulating AgPlts could be the underlying mechanism of the observed endothelium damage.

Microglia in the primate macula: specializations in microglial distribution and morphology with retinal position and with aging.

Microglia, the principal resident immune cell in the retina, play constitutive roles in immune surveillance and synapse maintenance, and are also associated with retinal disease, including those occurring in the macula. Perspectives on retinal microglia function have derived largely from rodent models and how these relate to the macula-bearing primate retina is unclear. In this study, we examined microglial distribution and cellular morphology in the adult rhesus macaque retina, and performed comparative characterizations in three retinal locations along the center-to-periphery axis (parafoveal, macular, and the peripheral retina). We found that microglia density peaked in the parafoveal retina and decreased in the peripheral retina. Individual microglial morphology reflected macular specialization, with macular microglia demonstrating the largest and most complex dendritic arbors relative to other retinal locations. Comparing retinal microglia between young and middle-aged animals, microglial density increased in the macular, but not in the peripheral retina with age, while microglial morphology across all locations remained relatively unchanged. Our findings indicate that microglial distribution and morphology demonstrate regional specialization in the retina, correlating with gradients of other retinal cell types. As microglia are innate immune cells implicated in age-related macular diseases, age-related microglial changes may be related to the increased vulnerability of the aged macula to immune-related neurodegeneration.

Natural history of postural instability in breast cancer patients treated with taxane-based chemotherapy: A pilot study.

Over 230,000 new cases of breast cancer are expected to be diagnosed in the United States in 2015. Taxane-based chemotherapy is often an effective treatment, but can also cause adverse symptoms in patients due to neurotoxicity. These side effects can impair postural control in patients; however, this instability has scarcely been quantified. The purpose of this pilot study was to gain insight into the natural history of postural instability in breast cancer patients being treated with taxane-based chemotherapy. Thirty-two breast cancer patients (31 female/1 male; 47.6±11.2 year; 16 stage II/16 stage III) completed eyes open and eyes closed quiet standing trials in the oncology clinic where they were being treated. These trials were collected at five timepoints throughout their chemotherapy treatment: (1) before initiating chemotherapy to provide a baseline, (2-4) before starting subsequent chemotherapy cycles, and (5) 1-3 months after receiving their last taxane infusion. After the first chemotherapy cycle, patients demonstrated increases in 95% confidence ellipse area of center of pressure (CoP) [45.2%, p=0.01] and root mean squared CoP excursion [18%, p=0.006] compared to baseline values for the eyes closed condition. These balance deficiencies progressed with cumulative taxane exposure. Postural instability persisted 1-3 months after completing chemotherapy with increases in 95% CoP ellipse area [86.8%, p=0.002], root mean squared CoP excursion [32.6%, p=0.001], and mean CoP velocity [30.4%, p=0.024]. The balance impairments demonstrated by patients in this study appear to be clinically relevant when compared to balance impairments previously reported in other patient populations.

Endocrine therapy in breast cancer: the neoadjuvant, adjuvant, and metastatic approach.

OBJECTIVES: To review the rationale for endocrine therapy in the neoadjuvant, adjuvant, and metastatic breast cancer setting and to highlight clinical considerations unique to this treatment. DATA SOURCES: Contemporary literature, clinical guidelines, and national statistics. CONCLUSION: Endocrine therapy represents an important strategy in the management of both early and advanced hormone positive breast cancer. Additional research is required to better define the role of neoadjuvant therapy and the optimal duration of treatment. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a pivotal role in the identification and management of endocrine therapy-associated symptoms. Prompt symptom intervention may improve therapy adherence and ultimately, may improve long-term disease outcomes.

Enduring and sex-specific effects of adolescent social isolation in rats on adult stress reactivity.

In adolescence, gender differences in rates of affective disorders emerge. For both adolescent boys and girls, peer relationships are the primary source of life stressors though adolescent girls are more sensitive to such stressors. Social stressors are also powerful stressors for non-human social species like rodents. In a rat model, we examined how social isolation during adolescence impacts stress reactivity and specific neural substrates in adult male and female rats. Rats were isolated during adolescence by single housing from day 30 to 50 of age and control rats were group housed. On day 50, isolated rats and control rats were re-housed in same-treatment same-sex groups. Adult female rats isolated as adolescents exhibited increased adrenal responses to acute and to repeated stress and exhibited increased hypothalamic vasopressin mRNA and BDNF mRNA in the CA3 hippocampal subfield. In contrast, adult male rats isolated as adolescents exhibited a lower corticosterone response to acute stress, exhibited a reduced state of anxiety as assessed in the elevated plus maze and reduced Orexin mRNA compared to adult males group-housed as adolescents. These data point to a markedly different impact of isolation experienced in adolescence on endocrine and behavioral endpoints in males compared to females and identify specific neural substrates that may mediate the long-lasting effects of stress in adolescence.