Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error.

A mismatch between optical power and ocular axial length results in refractive errors. Uncorrected refractive errors constitute the most common cause of vision loss and second leading cause of blindness worldwide. Although the retina is known to play a critical role in regulating ocular growth and refractive development, the precise factors and mechanisms involved are poorly defined. We have previously identified a role for the secreted serine protease PRSS56 in ocular size determination and PRSS56 variants have been implicated in the etiology of both hyperopia and myopia, highlighting its importance in refractive development. Here, we use a combination of genetic mouse models to demonstrate that Prss56 mutations leading to reduced ocular size and hyperopia act via a loss of function mechanism. Using a conditional gene targeting strategy, we show that PRSS56 derived from Müller glia contributes to ocular growth, implicating a new retinal cell type in ocular size determination. Importantly, we demonstrate that persistent activity of PRSS56 is required during distinct developmental stages spanning the pre- and post-eye opening periods to ensure optimal ocular growth. Thus, our mouse data provide evidence for the existence of a molecule contributing to both the prenatal and postnatal stages of human ocular growth. Finally, we demonstrate that genetic inactivation of Prss56 rescues axial elongation in a mouse model of myopia caused by a null mutation in Egr1. Overall, our findings identify PRSS56 as a potential therapeutic target for modulating ocular growth aimed at preventing or slowing down myopia, which is reaching epidemic proportions.

Extensive serous ciliochoroidal detachments and macular subretinal and intraretinal fluid following laser peripheral iridotomy.

Purpose: We present multimodal imaging of an interesting case of a 78-year-old man who developed large ciliochoroidal detachments and macular subretinal and intraretinal fluid in the right eye following bilateral neodymium-doped yttrium aluminium garnet (Nd:YAG) laser peripheral iridotomies (LPIs). Observations: The ciliochoroidal detachments developed in the absence of documented post-procedure hypotony or intraocular pressure fluctuation. Ultrasound biomicroscopy (UBM) confirmed serous ciliochoroidal detachment. There are a small number of cases of ciliochoroidal detachments developing after peripheral iridotomy, but these have involved either argon laser, significant decrease in intraocular pressure, or underlying ocular conditions or structural abnormalities, such as Vogt-Koyanagi-Harada (VKH) or nanophthalmos. Conclusions: Serous ciliochoroidal detachments following the relatively non-invasive procedure of LPI are rare occurrences. We present our case in hopes of increasing awareness of this potential acute complication. We also discuss the diagnostic challenges of this unique case, the extensive work up, and current status of the patient.

Mutations in a novel serine protease PRSS56 in families with nanophthalmos.

PURPOSE: Nanophthalmos is a rare genetic ocular disorder in which the eyes of affected individuals are abnormally small. Patients suffer from severe hyperopia as a result of their markedly reduced axial lengths, but otherwise are capable of seeing well unlike other more general forms of microphthalmia. To date one gene for nanophthalmos has been identified, encoding the membrane-type frizzled related protein MFRP. Identification of additional genes for nanophthalmos will improve our understanding of normal developmental regulation of eye growth. METHODS: We ascertained a cohort of families from eastern Canada and Mexico with familial nanophthalmos. We performed high density microsatellite and high density single nucleotide polymorphism (SNP) genotyping to identify potential chromosomal regions of linkage. We sequenced coding regions of genes in the linked interval by traditional PCR-based Sanger capillary electrophoresis methods. We cloned and sequenced a novel cDNA from a putative causal gene to verify gene structure. RESULTS: We identified a linked locus on chromosome 2q37 with a peak logarithm (base 10) of odds (LOD) score of 4.7. Sequencing of coding exons of all genes in the region identified multiple segregating variants in one gene, recently annotated as serine protease gene (PRSS56), coding for a predicted trypsin serine protease-like protein. One of our families was homozygous for a predicted pathogenic missense mutation, one family was compound heterozygous for two predicted pathogenic missense mutations, and one family was compound heterozygous for a predicted pathogenic missense mutation plus a frameshift leading to obligatory truncation of the predicted protein. The PRSS56 gene structure in public databases is based on a virtual transcript assembled from overlapping incomplete cDNA clones; we have now validated the structure of a full-length transcript from embryonic mouse brain RNA. CONCLUSIONS: PRSS56 is a good candidate for the causal gene for nanophthalmos in our families.

Transient myopic shift due to ciliary body detachment as the sole ocular manifestation of hypertensive emergency - A case report.

PURPOSE: Hypertensive emergency usually presents to ophthalmologists in the form of hypertensive retinopathy. We present a case of hypertensive emergency that presented as bilateral transient myopic shift due to ciliary body detachment in the absence of any retinal pathology. The purpose of this paper is to showcase another ocular manifestation of hypertensive emergency. OBSERVATIONS: A 35 year-old female with a blood pressure of 192/114 mmHg presented to the emergency department with headache and acute onset blurry vision. Computed Tomography (CT) of the head, and lumbar puncture were within normal limits. Visual acuity was counting fingers in the right eye and 6/90 in the left eye, both of which improved to 6/9 with -5.00 diopters spherical correction in the right eye, and -4.75 diopters correction in the left eye. Intraocular pressures were normal. Anterior chambers were shallow, and there were no retinal changes on dilated fundus examination. Enhanced-depth optical coherence tomography (EDI-OCT) showed bilateral increased choroidal thickness and ultrasound biomicroscopy (UBM) showed 360° ciliary body detachment with angle closure. With improved blood pressure control, her ciliary body detachment resolved and her refractive error returned to baseline. CONCLUSIONS: & Importance: Hypertensive emergency may present with choroidal thickening with anterior ciliary body rotation and detachment. A review of medications is important, as this presentation has also been reported as a rare side effect of sulphonamide drugs. In the absence of retinopathy, UBM and EDI-OCT imaging should be considered in the acutely hypertensive patient presenting with myopic shift.

The Halifax disaster (1917): eye injuries and their care.

Explosions, man-made and accidental, continue to require improved emergency medical responses. In the 1917 Halifax Explosion, an inordinate number of penetrating eye injuries occurred. A review of their treatment provides insight into a traumatic event with unique ophthalmological importance. Archived personal and government documents relating to the Halifax Explosion were reviewed at the Public Archives of Nova Scotia, Canada, along with a review of current literature. Twelve ophthalmologists treated 592 people with eye injuries and performed 249 enucleations. Sixteen people had both eyes enucleated. Most of the eye injuries were caused by shards of shattered glass. A Blind Relief Fund was established to help treat and rehabilitate the visually impaired. The injured were given pensions through the Canadian National Institute for the Blind, Toronto, Ontario, Canada, which continue to this day. Sympathetic ophthalmia was the feared complication for penetrating eye injuries and a common indication for enucleation in 1917. Even so, the severity and the overwhelming number of eye injuries sustained during the Halifax Explosion made it impossible for lengthy eye-saving procedures to be performed. Enucleation was often the only option.

Brachytherapy and anterior segment imaging in iris melanoma.

Ultrasound biomicroscopy (UBM) remains a potent tool in the diagnosis and characterization of uveal lesions. In the setting of malignancy, it can confirm both placement of and response to brachytherapy. We present a case of iris melanoma with aggressive BAP-1 mutation, treated successfully with I-131 brachytherapy which was both characterized and followed with UBM and thereafter discuss the current state of these modalities.

Brachytherapy and anterior segment imaging in iris melanoma.

A 40-year-old male presented to the ophthalmology clinic with a darkly pigmented infratemporal lesion in his right eye. The corrected visual acuity in both eyes was 6/6 and both pupils were equal and reactive. Slit lamp biomicroscopy showed a well-demarcated and heavily pigmented lesion in the peripheral iris between 6 and 8 o'clock. Ultrasound biomicroscopy (UBM) revealed a solid mass deriving from the iris stroma without ciliary body involvement, helping to classify the uveal melanoma and establishing the diagnosis of iris melanoma. Fine needle aspiration (FNA) confirmed melanoma with inactivation of the BAP1 gene. The patient was treated with brachytherapy using an I-125 plaque. Follow-up UBM, three years later, demonstrated significantly reduced dimensions of the tumour. UBM has become crucial to the differentiation of uveal melanomas from benign growths, and lesions <3 mm cannot be reliably visualised by other imaging modalities or localised to the correct uveal structure. Brachytherapy represents a safe and effective treatment option even in lesions that are BAP1 positive.

Extrascleral extension in association with ciliochoroidal melanoma: ultrasound biomicroscopy with histopathological correlation.

CASE REPORT: We present the case of a 71-year-old man with a melanoma arising from the ciliary body and extending into the choroid. Ultrasound biomicroscopy (UBM) revealed connection via an emissary canal to a subconjunctival nodule. Although evaluation for metastasis was negative at the time of diagnosis, multiple hepatic metastatic deposits were found 2 years post-enucleation. COMMENTS: It is crucial to identify the presence of scleral invasion and extrascleral extension for proper management planning in patients with choroidal melanomas. This case demonstrates that UBM is an accurate and useful tool for characterizing the morphologic pattern of scleral invasion of intraocular tumours.