The effects of female sex hormones on the human cornea across a woman's life cycle.

The cornea is a hormone-responsive tissue that responds to changing levels of female sex hormones. This review focuses on the structural and functional changes in the human cornea associated with the hormonal milestones of menarche, pregnancy, and menopause, as well as consequences stemming from the use of exogenous sex hormones for fertility control and replacement. Articles were identified by searching PubMed without language or region restrictions. The primary outcomes evaluated were changes in central corneal thickness (CCT), intraocular pressure (IOP), and quality of the ocular tear film. The potential impact of hormone-associated changes on the diagnosis and surgical management of common eye diseases, as well as the potential use of sex hormones as therapeutic agents is also considered. Understanding the physiological effects of female sex hormones on the cornea is important because that knowledge can shape the management decisions physicians and women face about ocular health across their life stages.

Efficacy and tolerability of nortriptyline in the management of neuropathic corneal pain.

PURPOSE: Neuropathic corneal pain (NCP) is a recently acknowledged disease entity. However, there is no consensus in potential treatment strategies, particularly in patients with a centralized component of pain. This study aims to assess the efficacy and tolerability of the tricyclic antidepressant, nortriptyline, among NCP patients. METHODS: Patients with clinically diagnosed NCP and a centralized component of pain, treated with oral nortriptyline, who had recorded pain scores as assessed by the ocular pain assessment survey at the first and last visit were included. Patients were excluded if they had any other ocular pathology that might result in pain or had less than 4 weeks of nortriptyline use. Demographics, time between visits, concomitant medications, systemic and ocular co-morbidities, duration of NCP, side effects, ocular pain scores, and quality of life (QoL) assessment were recorded. RESULTS: Thirty patients with a mean age of 53.1 ± 18.5 were included. Male to female ratio was 8:22. Mean ocular pain in the past 24 h improved from 5.7 ± 2.1 to 3.6 ± 2.1 after 10.5 ± 9.1 months (p < 0.0001). Twelve patients (40.0%) had equal to or more than 50% improvement, 6 patients (20.0%) had 30-49% improvement, 6 patients (20.0%) had 1-29% improvement, 4 patients (13.3%) did not improve, while 2 patients (6.7%) reported increase in pain levels. Mean QoL improved from 6.0 ± 2.5 to 4.3 ± 2.4 (p = 0.019). Eight patients (26.6%) discontinued treatment due to persistent side effects, despite improvement by 22.4%. CONCLUSION: Nortriptyline was effective in relieving NCP symptoms in patients with centralized component and insufficient response to other systemic and topical therapies who tolerated the drug for at least 4 weeks. Nortriptyline may be used in the management of patients with NCP.

Update on Diagnosis and Management of Conjunctival Papilloma.

Conjunctival papilloma is an acquired benign squamous cell tumor that can present at any age, but most frequently in the third and fourth decades of life. Papillomas have been associated with human papilloma virus (HPV) infection, usually types 6 and 11. Although histopathological diagnosis remains the gold standard, the advent of newer non-invasive imaging modalities such as optical coherence tomography (OCT) is transforming the way we diagnose and treat ocular surface tumors, including conjunctival papilloma. Management of these lesions can prove a challenge to the treating physician since not all lesions respond to medical and/or surgical therapy and in fact may worsen after surgical manipulation. In this review, the epidemiology, pathophysiology, clinical characteristics, and diagnosis of conjunctival papilloma including the use of OCT are discussed. Indications, efficacy, and side effects of currently available management options are also reviewed to guide the selection of the best treatment approach.

Scleral-sutured intraocular lenses: Single-surgeon technique for suture-preloaded intraocular lens insertion through a small-incision corneal wound.

For scleral intraocular lens (IOL) fixation, suture-loaded IOLs have traditionally been folded in half with a forceps and delivered intraocularly through 3.5 to 4.0 mm corneal wounds. We describe a technique in which a suture-loaded scleral IOL is inserted through a small-incision corneal wound using 2 widely available ocular surgery tools; that is, a C or D cartridge and a Bowman nasolacrimal duct probe. This technique is easy to replicate and can be performed without an assisting surgeon.

Efficacy of self-retained cryopreserved amniotic membrane for treatment of neuropathic corneal pain.

PURPOSE: Treatment of neuropathic corneal pain (NCP) remains intricate, and involves a long-term combined multistep approach. The self-retained cryopreserved amniotic membrane (PROKERA®, Bio-Tissue, Miami,FL) has been utilized for multiple ocular surface disorders. We evaluate the efficacy, safety, and tolerability of ProKera® Slim [PKS] and ProKera® Clear [PKC] in the treatment of NCP. METHODS: Retrospective case series of 9 patients who received PKS/PKC for the acute treatment of NCP. Patient demographics, prior therapies, clinical examination, duration of PKS/PKC retention, changes in pain severity, corneal subbasal nerve density and morphology by in vivo confocal microscopy (IVCM; HRT3/RCM, Heidelberg Engineering, Heidelberg, Germany), and adverse events were recorded. RESULTS: PKS/PKC were placed in 10 eyes of 9 patients. Pain severity improved by 72.5 ± 8.4% (from 6.3 ± 0.8 to 1.9 ± 0.6, scale 1-10, p = 0.0003) after retention for 6.4 ± 1.1 days. Despite shorter retention for 4.0 ± 0.7 days in patients with ring dysesthesia (4 eyes) or premature implant disengagement (2 eyes), pain severity still improved by 63.1 ± 12.5% (from 6.8 ± 1.0 to 2.4 ± 0.9, p = 0.009). During a follow-up of 9.3 ± 0.8 months, two patients reported recurrence of pain after 2.3 and 9.6 months respectively, treated effectively with additional PKS/PKC. IVCM showed a 36.6 ± 17.6% increase in total nerve density, from 17,700.9 ± 1315.7 to 21,891.3 ± 2040.5 µm/mm2 (p = 0.047), while the fellow PKS/PKC-untreated eyes did not show a significant interval change. Main nerve trunk and branch nerve densities were not statistically different. Dendritiform cell density decreased from 46.0 ± 8.2 to 32.0 ± 6.0 cells/mm2 (p = 0.01). CONCLUSIONS: PKS/PKC provide a safe and effective treatment approach to achieve sustained pain control in patients with NCP.

Pigmented Spindle Cell Nevus of Reed of the Eyelid.

PURPOSE: To report the clinical, pathological, and immunohistochemical features of the first pigmented spindle cell nevus (PSCN) of Reed documented to have appeared in the eyelid. METHODS: The findings of clinical and histopathological examination are presented, along with differential diagnoses and a review of the pertinent literature. CASE: A 3-year-old boy presented with a rapidly growing, heavily pigmented left lower lid papule raising the concern of malignancy, warranting excisional biopsy. Nests of predominantly junctional Mart-1-positive spindle cells were identified by histopathological examination. The cells were largely uniform in size, elongated, surrounded by granular and coarse melanin, with a Ki-67 proliferation index of 0-2%. Five-month follow-up did not evidence any recurrence or invasive behavior of this benign melanocytic tumor. CONCLUSION: This is the first documented case of PSCN of Reed, a distinct entity from Spitz nevus, presenting in the eyelid. The differential diagnoses include spindle cell and superficially spreading malignant melanoma as well as dysplastic nevus. Integration of clinical and histopathological findings with immunohistochemical and fluorescence in situ hybridization markers plays a central role in the diagnosis.

Serotonin receptor 2C regulates neurite growth and is necessary for normal retinal processing of visual information.

Serotonin (5HT) is present in a subpopulation of amacrine cells, which form synapses with retinal ganglion cells (RGCs), but little is known about the physiological role of retinal serotonergic circuitry. We found that the 5HT receptor 2C (5HTR2C) is upregulated in RGCs after birth. Amacrine cells generate 5HT and about half of RGCs respond to 5HTR2C agonism with calcium elevation. We found that there are on average 83 5HT+ amacrine cells randomly distributed across the adult mouse retina, all negative for choline acetyltransferase and 90% positive for tyrosine hydroxylase. We also investigated whether 5HTR2C and 5HTR5A affect RGC neurite growth. We found that both suppress neurite growth, and that RGCs from the 5HTR2C knockout (KO) mice grow longer neurites. Furthermore, 5HTR2C is subject to post-transcriptional editing, and we found that only the edited isoform's suppressive effect on neurite growth could be reversed by a 5HTR2C inverse agonist. Next, we investigated the physiological role of 5HTR2C in the retina, and found that 5HTR2C KO mice showed increased amplitude on pattern electroretinogram. Finally, RGC transcriptional profiling and pathways analysis suggested partial developmental compensation for 5HTR2C absence. Taken together, our findings demonstrate that 5HTR2C regulates neurite growth and RGC activity and is necessary for normal amplitude of RGC response to physiologic stimuli, and raise the hypothesis that these functions are modulated by a subset of 5HT+/ChAT-/TH+ amacrine cells as part of retinal serotonergic circuitry. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.

TARANTULA HAIR ASSOCIATED PANUVEITIS TREATED WITH SUSTAINED-RELEASE INTRAVITREAL DEXAMETHASONE IMPLANT.

PURPOSE: To report a case of tarantula hair-induced panuveitis treated with sustained-release intravitreal dexamethasone implant and followed by sequential spectral domain optical coherence tomography imaging. METHODS: Findings on clinical examination, anterior segment optical coherence tomography, corneal in vivo confocal microscopy, color fundus photos, fluorescein angiography, and retinal spectral domain optical coherence tomography are presented. Sequential optical coherence tomography images demonstrated the course of the chorioretinal lesions before and after sustained-release intravitreal dexamethasone implant. RESULTS: A 19-year-old female presented with localized temporal episcleritis and scleritis that incompletely resolved despite multiple courses of topical and oral corticosteroids. She subsequently developed focal vitritis and chorioretinitis, and was found to have tarantula hair-induced panuveitis. Anterior segment optical coherence tomography and in vivo confocal microscopy confirmed the presence of tarantula hairs embedded in the anterior corneal stroma. There was only transient improvement with posterior sub-Tenon's Kenalog injection. After treatment with sustained-release intravitreal dexamethasone implant, her symptoms improved and the chorioretinal lesions became inactive. Sequential spectral domain optical coherence tomography images revealed hyperreflective inner retina lesions that progressed to involve the outer retina, and then flattened to near resolution after therapy. CONCLUSION: This is the first case showing positive clinical outcomes supported by sequential retinal spectral domain optical coherence tomography using a sustained-release intravitreal dexamethasone implant to treat ophthalmia nodosa-induced by tarantula hairs.

The N-terminal Set-ß Protein Isoform Induces Neuronal Death.

Set-ß protein plays different roles in neurons, but the diversity of Set-ß neuronal isoforms and their functions have not been characterized. The expression and subcellular localization of Set-ß are altered in Alzheimer disease, cleavage of Set-ß leads to neuronal death after stroke, and the full-length Set-ß regulates retinal ganglion cell (RGC) and hippocampal neuron axon growth and regeneration in a subcellular localization-dependent manner. Here we used various biochemical approaches to investigate Set-ß isoforms and their role in the CNS, using the same type of neurons, RGCs, across studies. We found multiple alternatively spliced isoforms expressed from the Set locus in purified RGCs. Set transcripts containing the Set-ß-specific exon were the most highly expressed isoforms. We also identified a novel, alternatively spliced Set-ß transcript lacking the nuclear localization signal and demonstrated that the full-length (∼39-kDa) Set-ß is localized predominantly in the nucleus, whereas a shorter (∼25-kDa) Set-ß isoform is localized predominantly in the cytoplasm. Finally, we show that an N-terminal Set-ß cleavage product can induce neuronal death.

Unusually delayed presentation of persistent Descemet's membrane tear and detachment after cataract surgery.

A 51-year-old male who had undergone phacoemulsification in his left eye 11 months prior presented with complaint of sudden onset of blurred vision in the same eye. Review of his clinical course, slit-lamp exam, pachymetry, and specular endothelial microscopy led to the diagnosis of acute hydrops caused by Descemet's membrane dehiscence at the site of the incision. He was initially managed with medical treatment and observation. In the subsequent months of follow-up, the corneal edema and the patient's visual acuity did not improve. Intracameral gas injection was performed 7 months after presentation, but because of persistent corneal edema and nonattached Descemet's membrane, penetrating keratoplasty was performed. Histopathologic examination confirmed the diagnosis. The patient has had a clear corneal graft since then. Although Descemet's membrane detachment is a rather common complication after intraocular surgery, its unusually delayed presentation can also occur, and should not be confused with pseudophakic bullous keratopathy. Many mechanisms have been studied for the development of early tears and detachments after cataract surgery, but little is known about late presentations. The authors explore possible causes, and highlight the importance of instructing patients to avoid eye rubbing and any other type of trauma to the cornea after intraocular surgery.

Regulating Set-ß's Subcellular Localization Toggles Its Function between Inhibiting and Promoting Axon Growth and Regeneration.

The failure of the CNS neurons to regenerate axons after injury or stroke is a major clinical problem. Transcriptional regulators like Set-ß are well positioned to regulate intrinsic axon regeneration capacity, which declines developmentally in maturing CNS neurons. Set-ß also functions at cellular membranes and its subcellular localization is disrupted in Alzheimer's disease, but many of its biological mechanisms have not been explored in neurons. We found that Set-ß was upregulated postnatally in CNS neurons, and was primarily localized to the nucleus but was also detected in the cytoplasm and adjacent to the plasma membrane. Remarkably, nuclear Set-ß suppressed, whereas Set-ß localized to cytoplasmic membranes promoted neurite growth in rodent retinal ganglion cells and hippocampal neurons. Mimicking serine 9 phosphorylation, as found in Alzheimer's disease brains, delayed nuclear import and furthermore blocked the ability of nuclear Set-ß to suppress neurite growth. We also present data on gene regulation and protein binding partner recruitment by Set-ß in primary neurons, raising the hypothesis that nuclear Set-ß may preferentially regulate gene expression whereas Set-ß at cytoplasmic membranes may regulate unique cofactors, including PP2A, which we show also regulates axon growth in vitro. Finally, increasing recruitment of Set-ß to cellular membranes promoted adult rat optic nerve axon regeneration after injury in vivo. Thus, Set-ß differentially regulates axon growth and regeneration depending on subcellular localization and phosphorylation.