Nanophthalmos-Associated MYRF Gene Mutation Causes Ciliary Zonule Defects in Mice.

Purpose: Patients with nanophthalmos who undergo intraocular surgery often present with abnormal ciliary zonules. In a previous study, we reported mutation in MYRF that is implicated in the pathogenesis of nanophthalmos. The aim of this study was to model the mutation in mice to explore the role of MYRF on zonule structure and its major molecular composition, including FBN1 and FBN2. Methods: Human MYRF nanophthalmos frameshift mutation was generated in mouse using the CRISPR-Cas9 system. PCR and Sanger sequencing were used for genotype analysis of the mice model. Anterior chamber depth (ACD) was measured using hematoxylin and eosin-stained histology samples. Morphologic analysis of ciliary zonules was carried out using silver staining and immunofluorescence. Transcript and protein expression levels of MYRF, FBN1, and FBN2 in ciliary bodies were quantified using quantitative real-time PCR (qRT-PCR) and Western blot. Results: A nanophthalmos frameshift mutation (c.789delC, p.N264fs) of MYRF in mice showed ocular phenotypes similar to those reported in patients with nanophthalmos. ACD was reduced in MYRF mutant mice (MYRFmut/+) compared with that in littermate control mice (MYRF+/+). In addition, the morphology of ciliary zonules showed reduced zonular fiber density and detectable structural dehiscence of zonular fibers. Furthermore, qRT-PCR analysis and Western blot showed a significant decrease in mRNA expression levels of MYRF, FBN1, and FBN2 in MYRFmut/+ mice. Conclusions: Changes in the structure and major molecular composition of ciliary zonules accompanied with shallowing anterior chamber were detected in MYRFmut/+ mice. Therefore, MYRF mutant mice strain is a useful model for exploring pathogenesis of zonulopathy, which is almost elusive for basic researches due to lack of appropriate animal models.

Atypical free-floating iridociliary pigmented epithelial cysts and secondary glaucoma in a caiman (Caiman latirostris).

We describe a case of chronic ocular trauma that resulted in fixed and free-floating, pigmented epithelial iridociliary cysts, inflammation, and secondary glaucoma in a caiman (Caiman latirostris). A 20- to 25-year-old male caiman was presented with phthisis bulbi in the right eye, and congested episcleral vessels, corneal leukoma, disorganized anterior chamber, multifocal anterior synechia, and elevated intraocular pressure in the left eye. Ocular ultrasound of the left eye revealed round structures dispersed in the anterior and posterior chambers and vitreous cavity. Bilateral enucleation was performed, and gross pathology of the left eye revealed multiple pigmented cysts attached to the iris and posterior corneal surface causing marked distortion of the anterior uvea, and free-floating in the vitreous cavity. Histopathology demonstrated heavily pigmented cystic structures of iridociliary epithelium origin carpeting the anterior segment surfaces and causing obstruction of the iridocorneal angles, leading to secondary glaucoma. To the authors' knowledge, this is the first report of iridociliary cysts in wildlife species.

Ciliary Body Mass as a Feature of Ocular Sarcoidosis.

Importance: Ocular sarcoidosis may be the primary and only clinical manifestation of sarcoidosis, and irreversible loss of visual acuity may occur from delayed treatment. Thus, early diagnosis is imperative to preserve visual acuity. Establishing the diagnosis of sarcoidosis in cases manifesting only in the eye may require a diagnostic biopsy, which may prove challenging in the absence of available ocular surface, lacrimal gland, and systemic tissue for biopsy. Objective: To describe diffuse or segmental ciliary body mass as a clinical sign and tissue source for biopsy in the diagnosis of ocular sarcoidosis. Design, Setting, and Participants: This case series captures 3 cases from a university-based ocular oncology and uveitis practice. All 3 patients presented with uveitis and a diffuse or segmental ciliary body mass, which was identified via ultrasonographic biomicroscopy. Main Outcomes and Measures: Clinical, ancillary, and histopathological ocular findings in the 3 patients. Results: The patients were a 52-year-old white woman, a 42-year-old African American man, and an 81-year-old white man. Two individuals had unilateral involvement, and 1 had bilateral involvement. All 3 individuals presented with uveitis. Diffuse, circumferential ciliary body masses were observed in 2 patients. A localized, nodular ciliary body mass on the temporal quadrant with superior and inferior extensions was observed in 1 patient. Moderate to high internal reflectivity was observed on ultrasonographic biomicroscopy in all 3 individuals. Biopsies of the ciliary body masses were diagnosed as sarcoidosis in all 3 patients. Conclusions and Relevance: These findings support that diffuse or segmental ciliary body mass may serve as a clinical sign and tissue source for biopsy in the diagnosis of ocular sarcoidosis, although the frequency of this cannot be determined from 3 cases. To our knowledge, such cases all demonstrate a uveitic component; whether a ciliary body mass caused by sarcoidosis can occur in the absence of uveitis remains unknown.

Trifocal choroidal melanoma in an eye with oculodermal melanocytosis: A case report.

We report a case of trifocal choroidal melanoma (three separate tumors) in a 48-year-old Caucasian female who had been followed for oculodermal melanocytosis since childhood. At presentation, no tumor was present and annual examination was advised. Seventeen years later, three choroidal melanocytic lesions were detected in the right eye. Growth of each was documented, enucleation was performed, and histopathology revealed three independent choroidal melanomas. The patient developed extensive liver and bone metastases and subsequently died. Oculodermal melanocytosis is a risk factor for the development of uveal melanoma and a potential marker for worse prognosis. Careful long-term follow-up is required.

Bilateral Diffuse Uveal Melanocytic Proliferation Associated With Bladder Cancer: A Novel Imaging Finding.

The authors report a case of bilateral diffuse uveal melanocytic proliferation associated with transitional cell carcinoma of the bladder. A novel imaging finding on indocyanine green angiography of a "string of sausages" pattern in the large choroidal vessels is described. This occurs in areas of alternating retinal pigment epithelial hypertrophy and destruction, which is likely to be its cause. To the authors' knowledge, it has not been previously described. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:525-528.].

Corneal Endothelial Cell Density in Uveal Coloboma Associated With Microcornea.

PURPOSE: To evaluate the relationship between endothelial cell density (ECD) and mean corneal diameter (MCD) in eyes with uveal coloboma associated with microcornea. METHODS: Corneal endothelial cell imaging was performed using specular microscopy on 22 eyes of 18 subjects diagnosed with uveal coloboma associated with microcornea. The MCD was noted as the average of horizontal and vertical corneal diameters, which were measured using the ruler tool of the slit-lamp biomicroscope and Castroviejo calipers. RESULTS: Mean age of the study subjects was 29.7 ± 10.4 years (range, 14-46 years). The MCD was 7.3 ± 1.1 mm (range, 4.9-9 mm). Mean ECD (3436 ± 316.2 cells/mm) of the study subjects was significantly (P < 0.0001) higher than the mean ECD (2761.8 ± 140.9 cells/mm) of age-matched (range, 10-40 years) normal eyes with no ocular pathology. The pleomorphism and polymegathism were comparable between the 2 groups. Regression analysis showed that MCD had a significant negative (R = -0.55; P = 0.02) relationship with ECD. CONCLUSIONS: Eyes with congenital uveal coloboma associated with microcornea have increased ECD. Increased ECD may be partly due to a reduced posterior corneal surface area in microcornea.

Implantable collamer lens surgery in patients with primary iris and/or ciliary body cysts.

BACKGROUND: The prevalence of primary iris and/or ciliary body cysts is common in myopia, though asymptomatic in nearly all cases. It's a very valuable thing to study the clinical safety and reliability of implantable collamer lens (ICL) surgery in patients with primary iris and/or ciliary body cysts. METHODS: A total of 108 patients (201 eyes) were included in this retrospective study. All eyes had been implanted with V4c implantable collamer lens (ICLV4c). According to the eyes with or without primary iris and/or ciliary body cysts, all eyes were divided into two groups. We observed preoperative and postoperative uncorrected distance visual acuity (UDVA), corrected distance visual acuity)(CDVA), intra-ocular pressure(IOP), anterior chamber volume(ACV), anterior chamber depth(ACD), trabecular-iris angle (TIA), angle opening distance at 500 µm (AOD500),vertical central distance between the corneal endothelium and the front surface of ICL(CE-ICL), and the central vault. The follow-up periods covered 12 months. RESULTS: Among all the 201 eyes, primary iris and/or ciliary body cysts were detected in 54 eyes (26.87%),but the prevalence was account to 36.11%(18males,21females).There were 30 eyes (55.56%) with unilateral single cyst, 12 eyes (22.22%) with unilateral double cysts, 12 eyes (22.22%) eyes with unilateral multiple and/or multi-quadrants cysts, the mean size of cysts was (0.714 ± 0.149)mm(range from 0.510 to 1.075 mm).30.4% of the cysts were located at iridociliary sulcus, 65.5% in pars plicata, and 4.1% in midzonal iris, which showed a characteristic distribution pattern, with cysts found predominantly in the inferior and temporal quadrants.The postoperative size and the number of cysts showed nearly no changes. The postoperative ACV, AOD500 and TIA showed a statistical reduction in both two groups (P < 0.05), but with no statistical significant between the two groups (P > 0.05), the parameters of postoperative IOP,CE-ICL and central vault also showed the same results as which. We did not observe serious complication and IOP elevating in the whole follow-up periods. CONCLUSION: Primary iris and/or ciliary body cysts are not absolutely contraindication for ICL surgery. For some single cyst smaller than 1.075 mm or single quadrant cysts located at ciliary body are rare to lead some serious complications. But, for some multiple cysts, especially multi-quadrants cysts located at iridociliary sulcus, we still should remain cautions.

Corneal thickness in uveal coloboma with microcornea.

PurposeTo evaluate the relationship between central corneal thickness (CCT) and horizontal corneal diameter (HCD) in eyes with uveal coloboma and microcornea.Patients and methodsAll adult patients with uveal coloboma having microcornea in at least one eye and seen between May 2014 and July 2016 at the cataract clinic of our tertiary eye care center were evaluated. The study group comprised 26 colobomatous eyes of 15 patients who had associated microcornea. The control group comprised eyes with uveal coloboma and normal-sized cornea (n=12 eyes of 9 patients). The main outcome measure included the relationship between CCT and HCD in eyes with uveal coloboma and microcornea.ResultsThe mean HCD of the study and control groups was 6.97±1.28 and 11.39±0.67 mm, respectively. The mean central pachymetry of the study group was 668.4±40.2 µm compared with 555.3±41.8 µm in the control group. In both the groups, CCT was negatively correlated with HCD (R=-0.62 in the study group and R=-0.72 in the control group).ConclusionsUveal colobomatous eyes with microcornea have thicker corneas compared with uveal colobomatous eyes with normal diameter corneas that have normal central corneal thickness. In all the eyes with uveal coloboma, there is a negative correlation between horizontal corneal diameter and central corneal thickness.

Bilateral diffuse uveal melanocytic proliferation: Case report and literature review.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic intraocular disease that causes progressive visual loss in patients driven by an IgG factor associated with an underlying malignancy. Characteristic ocular findings include exudative retinal detachment, rapid cataract formation and uveal melanocytic tumours. The awareness and documentation of BDUMP has increased during the past decade, and the increasing amount of data collected demonstrates the effect of treatment with plasmapheresis and the value of diagnostic tools in BDUMP such as genetic and immunologic investigations. The literature of BDUMP has not been reviewed since 2003, and there is a growing need for an updated review on diagnosis and management of BDUMP. We review the literature and report a case of BDUMP with a white ciliary body tumour, iris rubeosis, increased iris pigmentation and cataract.

Characterisation of choroidal morphological and vascular features in diabetes and diabetic retinopathy.

AIM: We aimed to characterise specific morphological and vascular features of the choroid in Indian adults with diabetes and diabetic retinopathy (DR). METHODS: Consecutive participants from the Singapore Indian Eye Study's 6-year follow-up examination underwent choroidal imaging using spectral domain optical coherence tomography (OCT) with enhanced depth imaging. Raw OCT images were loaded on a custom-written application on MATLAB that enabled delineation for detailed morphological and vascular analyses. Multiple linear regression analyses were performed to assess differences in choroidal characteristics by diabetes DR. RESULTS: Of the 462 recruited participants, 273 had no diabetes (mean age was 60.1±6.8 years), 100 had diabetes but no DR (61.8±7.4 years) and 89 had DR (62.4±6.0 years). In multiple regression analysis, after accounting for relevant confounders, compared with those without diabetes, participants with diabetes had significantly thinner mean choroidal thickness (CT; mean difference (MD)=-25.19 µm, p=0.001), smaller choroidal volume (MD=-0.23 mm3, p=0.003), more inflection points (MD=1.78, p<0.001) and lesser choroidal vascular area within the foveal (MD=-0.024 mm2, p=0.001) and macular (MD=-0.095 mm2, p<0.001) regions. Among the diabetic group, subjects with DR had significantly thicker mean CT (MD=25.91 µm, p=0.001), greater choroidal volume (MD=0.24 mm3, p=0.009), lesser inflection points (MD=-0.478, p=0.045) and greater choroidal vascular area at foveal (MD=0.016 mm2, p=0.019) and macular (MD=0.057 mm2, p=0.016) regions, compared with those without DR. CONCLUSIONS: Choroidal morphology and vasculature were altered in Indian adults with diabetes and DR. These findings may provide insights into choroidal changes in diabetes and DR.

Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony.

Progressive hemifacial atrophy (PHA) is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.

Unilateral choroidal granulomas complicated by choroidal neovascular membrane treated successfully with intravitreal triamcinolone in a patient with sarcoidosis.

This case describes the use of intravitreal triamcinolone in the treatment of unilateral choroidal granulomas secondary to systemic sarcoidosis complicated by choroidal neovascular membrane. A single injection of 2 mg intravitreal triamcinolone was administered as treatment for rapidly progressing choroidal granulomas and associated choroidal neovascular membrane with subretinal fluid. Visual acuity had dropped from 6/5 to 6/48 with the progressing lesions. The patient was a 52-year-old woman with type 2 diabetes mellitus who was reluctant to consider oral steroids in view of their side effect profile. Ten days after injection, visual acuity improved to 6/24 and to 6/6 at 3 months follow-up with resolution of the subretinal fluid. There was no rise in intraocular pressure. There has been no recurrence at 5 months follow-up.

Medical therapy for uveal effusion syndrome.

PURPOSE: To report a case series of three patients with bilateral uveal effusion syndrome (UES), treated conservatively with oral carbonic anhydrase inhibitors and topical prostaglandin analogues (PAs). METHODS: Three patients with bilateral UES were treated with the same initial therapy. Topical PA latanoprost 0.005% and acetazolamide 250 mg were administered in order to reduce intraocular pressure, improve uveoscleral outflow, and facilitate resolution of uveal effusion. RESULTS: The chorioretinal detachment resolved within 3 months in two reported patients while the third one underwent surgery on his left eye. After clinical improvement, further oral therapy with acetazolamide was stopped, while topical prostaglandins were continued for at least the next 3 months. All patients were free from recurrence during the follow-up period. CONCLUSION: Although the usually recommended UES therapy is partial or full-thickness sclerectomy, our case series showed apparent resolution of chorioretinal detachment in two patients on medical therapy alone. Conservative therapy may be the first step before the standard recommended surgical approach, but further studies are needed to verify the effectiveness of reported therapy.

Tissue-resident exhausted effector memory CD8+ T cells accumulate in the retina during chronic experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis is a model for noninfectious posterior segment intraocular inflammation in humans. Although this disease is CD4(+) T cell dependent, in the persistent phase of disease CD8(+) T cells accumulate. We show that these are effector memory CD8(+) T cells that differ from their splenic counterparts with respect to surface expression of CD69, CD103, and Ly6C. These retinal effector memory CD8(+) T cells have limited cytotoxic effector function, are impaired in their ability to proliferate in response to Ag-specific stimulation, and upregulate programmed death 1 receptor. Treatment with fingolimod (FTY720) during the late phase of disease revealed that retinal CD8(+) T cells were tissue resident. Despite signs of exhaustion, these cells were functional, as their depletion resulted in an expansion of retinal CD4(+) T cells and CD11b(+) macrophages. These results demonstrate that, during chronic autoimmune inflammation, exhausted CD8(+) T cells become established in the local tissue. They are phenotypically distinct from peripheral CD8(+) T cells and provide local signals within the tissue by expression of inhibitory receptors such as programmed death 1 that limit persistent inflammation.

Dermal and conjunctival melanocytic proliferations in diffuse uveal melanocytic proliferation.

AIM: The goal of this case report is to describe the dermatologic and conjunctival findings in a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), a paraneoplastic syndrome usually associated with gynecologic cancers. There is little information about other dermatologic melanocytic findings in these patients. METHODS: Histologic and fluorescent in situ hybridization (FISH) analysis of three separate skin biopsies, one of which was separated by 21 months from the others, were performed in a 71-year-old patient with BDUMP to assess for histologic and chromosomal abnormality. Conjunctival histologic evaluation was also done. RESULTS: Dermal melanocytic proliferation was seen in each specimen. The cells were spindle type with mitotic activity. FISH analysis showed a normal copy of chromosomes. The conjunctival sample also showed normal FISH analysis. CONCLUSION: BDUMP is associated with multifocal dermal and conjunctival melanocytic proliferation.

A modified ultrasound-guided surgical technique for the management of the uveal effusion syndrome in patients with normal axial length and scleral thickness.

PURPOSE: The purpose of this study was to describe a modified surgical technique for the management of the uveal effusion syndrome (UES). METHODS: A consecutive interventional case series of six eyes with UES is reported. The diagnosis of the UES was based on detailed ophthalmic examination, fluorescein angiography, B-scan ultrasonography, biometry, and magnetic resonance imaging. All eyes underwent an ultrasound-guided placement of the sclerostomies subjacent to the area of maximal choroidal swelling using a scleral punch without scleral flaps or vortex vein decompression. RESULTS: All patients were men with a mean age of 53 years. The mean postoperative follow-up was 16.25 months. Five eyes had normal axial lengths (22.54-23.05 mm) by ultrasound and normal sclera thickness on magnetic resonance imaging. One eye had a shorter axial length (21.65 mm) and mild scleral thickening on magnetic resonance imaging. All six eyes had anterior peripheral choroidal swelling. Three eyes had associated serous retinal detachment, and three eyes had acute appositional angles. After surgery, five eyes had total resolution of the peripheral choroidal swelling and retinal detachment or normalization of the angle. One eye had partial resolution of the retinal detachment. Of the three eyes with retinal detachment, two eyes experienced improvement in visual acuity after surgery. No complications were noted. CONCLUSION: This modified ultrasound-guided surgical technique for sclerostomy placement seems to be effective in the management of the UES, including eyes with normal axial length and scleral thickness, a subset of the UES that has been previously reported not to respond to surgery.

[Leopard-spot pattern in fluorescein angiography]. / Leopardenmuster in der Fluoreszenzangiographie.

The uveal effusion syndrome is a rare disease characterized by serous choroidal detachment. The pathogenesis of idiopathic uveal effusion syndrome has not yet been conclusively established. One hypothesis is an abnormality of diffusion of extravascular proteins in the choroid leading to decompensation of the pigment epithelium pumping capacity. Fluid then accumulates in the subretinal space leading to retinal detachment which results in loss of visual acuity. It typically affects males and hypermetropia is another risk factor. When looking at the fundus a circular serous detachment of the choroid and choroidal puckering is typical. The fluorescein angiography shows hyperfluorescence in the form of a leopard-spot pattern. Space-occupying lesions have to be excluded with the help of ultrasound or magnetic resonance tomography. The uveal effusion syndrome is a diagnosis by exclusion. Treatment varies because of the different hypotheses for the pathogenesis. An intraocular tamponade in combination with laser coagulation may for example be an effective treatment.