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AimsTo characterise and classify the morphological, clinical and tomographic characteristics of focal choroidal excavation (FCE) lesions to determine their prognostic implications.Methods36 eyes with FCE (32 patients) underwent multimodal imaging, including spectral domain optical coherence tomography and fundus autofluorescence. FCE lesions were classified into three subtypes: (1) type 1: myopic (central choroidal thickness: 200 µm, with associated chorioretinal pathology).Results80.6% of eyes were followed longitudinally (26.8±18.8 months). There were 9 type 1 FCEs (myopic), 8 type 2 FCEs (U-shaped, congenital) and 19 type 3 FCEs (V-shaped, secondary). Type 2 FCEs trended towards larger maximum widths (p=0.0563). Type 3 FCEs were associated with central serous chorioretinopathy or pachyvessels (47.4%), but were also seen in pattern dystrophy, geographic atrophy, inactive choroiditis, torpedo maculopathy and adult-onset vitelliform dystrophy. Choroidal neovascular membranes (CNVMs) were more prevalent in type 3 FCE (41.2% compared with 11.1% for type 1 FCE, p=0.251, and 0% for type 2 FCE, p=0.043).ConclusionsThe FCE types, stratified by central choroidal thickness, demonstrated distinct morphological characteristics and associated findings. The classification scheme held prognostic implications as type 3 FCE with V shapes were associated with other chorioretinal conditions and were more likely to develop CNVM.

Local translation can provide a rapid, spatially targeted supply of new proteins in distal dendrites to support synaptic changes that underlie learning. Learning and memory are especially sensitive to manipulations of translational control mechanisms, particularly those that target the initiation step, and translation initiation at synapses could be a means of maintaining synapse specificity during plasticity. Initiation predominantly occurs via recruitment of ribosomes to the 5’ mRNA cap by complexes of eukaryotic initiation factors (eIFs), and the interaction between eIF4E and eIF4G1 is a particularly important target of translational control pathways. Pharmacological inhibition of eIF4E-eIF4G1 binding impairs formation of memory for aversive Pavlovian conditioning as well as the accompanying increase in polyribosomes in the heads of dendritic spines in the lateral amygdala (LA). This is consistent with a role for initiation at synapses in memory formation, but whether eIFs are even present near synapses is unknown. To determine whether dendritic spines contain eIFs and whether eIF distribution is affected by learning, we combined immunolabeling with serial section transmission electron microscopy (ssTEM) volume reconstructions of LA dendrites after Pavlovian conditioning. Labeling for eIF4E, eIF4G1, and eIF2α – another key target of regulation – occurred in roughly half of dendritic spines, but learning effects were only found for eIF4E, which was upregulated in the heads of dendritic spines. Our results support the possibility of regulated translation initiation as a means of synapse-specific protein targeting during learning and are consistent with the model of eIF4E availability as a central point of control.

Purpose To report refractive outcomes of scleral-fixated intraocular lens (IOL) implantation with Gore-Tex (W.L. Gore & Associates, Newark, DE) suture and combined pars plana vitrectomy and compare predicted refractive outcomes among 5 IOL power calculation formulas. Design Retrospective case series. Participants Patients undergoing scleral-fixated IOL implantation with Gore-Tex suture at our institution between January 2015 and June 2018. Methods Comparison of preoperative biometrics with postoperative refraction and calculation of predicted refractive outcome with 5 different IOL formulas. Main Outcome Measures Prediction error and absolute error to compare postoperative refraction with refraction predicted by lens power calculation formulas. Results Thirty-one eyes of 31 patients were included. All power calculations assumed in-the-bag position of the IOL. The Akreos A060 (Bausch & Lomb, Rochester, NY) was implanted in 23 eyes and the CZ70BD (Alcon, Fort Worth, TX) in 8 eyes, and all lenses were sutured 3 mm behind the limbus. Average postoperative spherical equivalent (SE) was –0.79±0.95 diopters (D). Average prediction error (postoperative SE refraction minus target refraction) was –0.19±0.72 D. Postoperative SE was within 1.0 D of target in 25 of 31 patients (81%) and 2.0 D of target in 31 of 31 patients (100%). The repeated-measures analysis of variance of absolute error by lens power formula was significant (P = 0.012), with Haigis demonstrating greater error. There was no significant difference among Barrett II, Sanders-Retzlaff-Kraff theoretical (SRK/T), Holladay 2, or Hoffer Q. Conclusions For eyes undergoing pars plana vitrectomy with scleral-sutured IOL implantation, assumption of in-the-bag IOL position when calculating lens power leads to acceptable refractive outcomes. Barrett II, SRK/T, Holladay 2, and Hoffer Q formulas were noninferior to each other.

Local translation can provide a rapid, spatially targeted supply of new proteins in distal dendrites to support synaptic changes that underlie learning. Learning and memory are especially sensitive to manipulations of translational control mechanisms, particularly those that target the initiation step, and translation initiation at synapses could be a means of maintaining synapse specificity during plasticity. Initiation predominantly occurs via recruitment of ribosomes to the 5’ mRNA cap by complexes of eukaryotic initiation factors (eIFs), and the interaction between eIF4E and eIF4G1 is a particularly important target of translational control pathways. Pharmacological inhibition of eIF4E-eIF4G1 binding impairs consolidation of memory for aversive Pavlovian conditioning as well as the accompanying increase in polyribosomes in the heads of dendritic spines in the lateral amygdala (LA). This is consistent with a role for initiation at synapses in memory formation, but whether eIFs are even present near synapses is unknown. To determine whether dendritic spines contain eIFs and whether eIF distribution is affected by learning, we combined immunolabeling with serial section transmission electron microscopy (ssTEM) volume reconstructions of LA dendrites after Pavlovian conditioning. Labeling for eIF4E, eIF4G1, and eIF2α – another key target of regulation – occurred in roughly half of dendritic spines, but learning effects were only found for eIF4E, which was upregulated in the heads of dendritic spines. Our results support the possibility of regulated translation initiation as a means of synapse-specific protein targeting during learning and are consistent with the model of eIF4E availability as a central point of control.

Scleral buckling is a method of reattaching the neurosensory retina to the retinal pigment epithelium when retinal detachment occurs. While the buckle procedure has high success rates in terms of reattaching the retina, the forces created by encircling and segmental buckles can alter the biomechanical properties of the eye and many of its structures, including axial length, corneal power, astigmatism, corneal hysteresis, corneal resistance factor, anterior chamber depth, ocular volume, ocular rigidity, and ocular blood flow. This chapter delves into the biomechanical changes induced by scleral buckling.

Purpose: The purpose of this article is to examine the clinical outcomes of scleral fixation of intraocular lenses (IOLs) using Gore-Tex suture at our institution. Methods: A retrospective chart review was conducted of patients who underwent scleral fixation of an IOL with Gore-Tex suture with concurrent pars plana vitrectomy. Intraoperative and postoperative complications were assessed. Results: Seventy-four eyes of 74 patients were included with a mean follow-up interval of 210 days (range, 33–720 days). The mean best-corrected visual acuity improved from 20/480 (1.38 logarithm of the minimum angle of resolution [logMAR]) preoperatively to 20/78 (0.59 logMAR) postoperatively ( P < .001). Indications included dislocated lens implant (42), aphakia without capsular support (18), and subluxation of crystalline lens (14). Bausch and Lomb Akreos AO60 IOL was implanted in 52 eyes, Alcon CZ70BD in 15, and Bausch and Lomb enVista MX60 in 6. Postoperative complications included temporary ocular hypertension in 9 eyes (12%), temporary hypotony in 7 (9%), cystoid macular edema in 3 eyes (4%), corneal decompensation in 2 eyes (3%), IOL dislocation requiring exchange in 1 case (1.4%), vitreous hemorrhage in 2 cases (3%), and retinal detachment in 2 cases (3%). There were no cases of postoperative suture breakage or erosion, endophthalmitis, or hyphema. Conclusions: The use of Gore-Tex suture in scleral fixation of posterior chamber IOLs was well tolerated at a mean follow-up interval of 210 days. There were no suture-related complications.

This opening chapter describes the evaluation and management of three patients with increasing severity of aqueous-deficient dry eye disease (AD-DED) (the management of meibomian gland disease, which frequently coexists with aqueous deficiency, is discussed in Chap. 2). The diagnosis and management of these three cases follows the Dry Eye Workshop (DEWS) recommendation which is based on the severity levels (Table 1.1). In Case 1, with mild dry eye disease (severity level 1), the emphasis is on proper history and counseling with lifestyle modifications. Case 2, with more moderate disease (severity level 2), highlights the use of anti-inflammatory therapy and the option of punctal plugs. Case 3, with more severe disease (severity level 3), discusses the advanced treatment options including total punctal occlusion, serum tears, and scleral lenses.

Aqueous tear-deficient dry eye is a multifactorial chronic disorder in which the lacrimal glands fail to produce enough tears to maintain a healthy ocular surface. The existence of lacrimal gland stem/progenitor cells was proposed in several species, yet their origin and characteristics are not very clear. Here, we investigated the presence of resident progenitor cells and their regenerative potential in a rabbit model with lacrimal gland main excretory duct ligation-induced injury. The ligation-injured lacrimal glands temporarily decreased in weight and had impaired tear secretion. Protein expression profiles and transcriptional profiles were obtained from injured tissue. Isolated lacrimal gland progenitor cells were tested and characterized by stem cell-related marker evaluation, single cell clonal assay and three-dimensional (3-D) culture. The results of our study indicate that lacrimal glands are capable of tissue repair after duct ligation-induced injury, likely involving resident stem/progenitor cells and epithelial-mesenchymal transitions. Lacrimal gland progenitor cells isolated from ligated tissue can differentiate in 3-D culture. The results provide further insights into lacrimal gland stem/progenitor cell physiology and their potential for treating severe cases of tear deficiency.

Varying degrees of optic neuropathy can be seen in patients with Charcot-Marie-Tooth (CMT) disease. To define and characterize the extent of optic neuropathy in patients with CMT2A and CMT1A, two patients from both sub-classifications were evaluated. All patients underwent complete neuro-ophthalmic examinations, and optical coherence (OCT) measurements of the retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) were obtained, along with pattern visual evoked potential (VEP) and pattern electroretinogram (ERG) recordings. RNFL thickness measurements were decreased in both patients with CMT2A, and normal in both patients with CMT1A. GCC measurements were decreased in both patients with CMT2A, mildly decreased in one patient with CMT1A and normal in the second CMT1A patient. VEP latencies were delayed in one patient with CMT2A and one patient with CMT1A. VEP latencies were immeasurable in the other CMT2A patient and not obtained in the second CMT1A patient. Pattern ERG P50-N95 amplitudes were decreased in both patients with CMT2A and normal in one patient with CMT1A. The pattern ERG was immeasurable in the second patient with CMT1A. The pattern of RNFL and GCC thinning in CMT2A with optic neuropathy, a subset of HMSN VI, closely resembles that seen in other mitochondrial optic neuropathies.

Translation in dendrites is believed to support synaptic changes during memory consolidation. Although translational control mechanisms are fundamental mediators of memory, little is known about their role in local translation. We previously found that polyribosomes accumulate in dendritic spines of the adult rat lateral amygdala (LA) during consolidation of aversive pavlovian conditioning and that this memory requires cap-dependent initiation, a primary point of translational control in eukaryotic cells. Here we used serial electron microscopy reconstructions to quantify polyribosomes in LA dendrites when consolidation was blocked by the cap-dependent initiation inhibitor 4EGI-1. We found that 4EGI-1 depleted polyribosomes in dendritic shafts and selectively prevented their upregulation in spine heads, but not bases and necks, during consolidation. Cap-independent upregulation was specific to spines with small, astrocyte-associated synapses. Our results reveal that cap-dependent initiation is involved in local translation during learning and that local translational control varies with synapse type.SIGNIFICANCE STATEMENTTranslation initiation is a central regulator of long-term memory formation. Local translation in dendrites supports memory by providing necessary proteins at synaptic sites, but it is unknown whether this requires initiation or bypasses it. We used serial electron microscopy reconstructions to examine polyribosomes in dendrites when memory formation was blocked by an inhibitor of translation initiation. This revealed two major pools of polyribosomes that were upregulated during memory formation: one pool in dendritic spine heads that was initiation dependent and another pool in the bases and necks of small spines that was initiation independent. Thus, translation regulation differs between spine types and locations, and translation that occurs closest to individual synapses during memory formation is initiation dependent.

Aqueous tear-deficient dry eye disease is a multifactorial chronic disorder, in which the lacrimal gland fails to produce enough tears to maintain a healthy ocular surface. Some severe cases may develop corneal damage and significant vision loss. Treatment primarily involves palliation using ocular surface lubricants, but can only provide temporary relief. Construction of a bioengineered lacrimal gland having functional secretory epithelial cells is a potentially promising option for providing long-term relief to severe dry eye patients. Using sphere-forming culture techniques, we cultured adult rabbit lacrimal gland progenitor cells and prepared a lacrimal gland scaffold by decellularization. When progenitor cells were seeded onto the decellularized scaffold, they formed duct- and acinar-like structures in the three-dimensional culture system. Lacrimal gland epithelial cells showed good cell viability, cell differentiation, and secretory function in decellularized lacrimal gland matrix, as indicated by morphology, immunostaining, and β-hexosaminidase secretion assay. This study demonstrated the potential suitability of utilizing tissue-specific progenitor cells and a tissue-derived bioscaffold for lacrimal gland restoration.