Taiwan Journal of Ophthalmology最新文献

The molecular landscape of numerous human malignancies has been elucidated since the advances in sequencing techniques. However, unlike their cutaneous counterparts, which have a higher incidence and more affected patients as study subjects, conjunctival melanocytic neoplasms are less studied, with evidence mainly restricted to case reports or case series. This review aims to summarize and update findings on genetic alterations in conjunctival melanocytic lesions based on the diagnoses listed in the fifth edition of the World Health Organization classification of the tumors of the eye. These include conjunctival common nevus, conjunctival blue nevus, conjunctival WNT-activated deep penetrating/plexiform melanocytoma (nevus), conjunctival melanocytic intraepithelial lesions, and conjunctival melanoma. We also review the role of genetic alterations in the development and progression of conjunctival melanoma. Furthermore, we compare the genetic alterations of conjunctival melanoma with those of cutaneous melanoma and discuss specific targeted therapies such as BRAF inhibitors, MEK inhibitors, and immunotherapies for localized advanced or metastatic conjunctival melanoma. In conclusion, this article reviews recent advances in genetic alterations and associated treatment strategies for conjunctival melanocytic lesions, including benign, premalignant, and malignant diseases. The similarities between conjunctival and cutaneous melanoma may shed a light on future studies and clinical trials focused on conjunctival melanoma.

In this study, we report a rare case of retinal vascular proliferation (RVP) in von Hippel-Lindau (VHL) disease, followed by a literature review. A 12-year-old boy presented with a left cerebellar hemangioblastoma and right eye blurred vision for 1-2 years. Fundus examination found no capillary hemangioblastoma lesion but a broad epiretinal fibrovascular membrane, which caused significant traction to the right macula. The genetic testing identified a pathogenic missense mutation (c. 223A > G) within the VHL gene, confirming VHL disease. RVP is a less common, poorly understood condition that can occur in VHL disease apart from the typical retinal capillary hemangioblastoma. The surface vasculature of the fibrovascular membrane regressed over an observation period of 3 years, and pars plana vitrectomy was eventually conducted at the age of 15 years to remove the fibrovascular membrane. Nevertheless, his visual acuity remained at 20/200 at postoperative 1 year due to the development of cataracts. In our literature review, we analyzed 39 reported cases of RVP, of which 90% had unilateral lesions, 70% had lesions at the juxtapapillary location, and 50% had a visual acuity <20/40. The mean onset age was 24 years. An intervention was performed in 39% of the cases and 78% experienced improved vision posttreatment. In conclusion, RVP likely starts as mainly vascular proliferation and eventually regresses spontaneously to fibrotic tissue formation. Unlike typical retinal capillary hemangioblastoma, vision can improve after an intervention, even in eyes with juxtapapillary lesions.

Plaque brachytherapy plays an essential role in the management of intraocular tumors, allowing localized treatment while minimizing damage to surrounding structures. Since the earliest reports of sutured radon seeds used in glioma treatment in the 1920s, plaque brachytherapy in the field of ocular oncology has continued to expand and improve significantly. Today, a wide variety of ocular conditions, both oncologic and not can be treated using plaque brachytherapy. Continued innovations have also improved clinical safety and efficacy for both providers and patients alike. The use of new radioisotopes, combined with continued refinement in plaque design and applicators alongside radiation dose planning are some of novel methods used to maximize coverage and reduce radiation exposure to critical eye structures. In this paper, we will discuss promising future developments that will continue to revolutionize treatment.

Choroidal osteoma is a rare, slow-growing intraocular osseous tumor. Limited information is available regarding the management of tumors growing toward the fovea. In this study, we present two cases of growing choroidal osteoma that were successfully treated with proton beam radiation therapy. In one case, tumor growth toward the fovea in a 12-year-old female was treated with proton beam radiation as the primary intervention. In the other, proton beam radiation was used after photodynamic therapy failed to control tumor growth in a 16-year-old female with choroidal osteoma. Both cases demonstrated sustained tumor growth cessation for 42 and 38 months, respectively. Low-dose proton beam radiation appears to be an effective treatment option to halt tumor growth and preserve vision, though long-term follow-up is essential.

Purpose: Cysteine-rich 61 (Cyr61) may enhance angiogenesis and inflammation in diabetic retinopathy (DR). Cyclooxygenase-2 (COX-2) is an immediate-early gene product of inflammation and it also plays an important role in developing DR. We aim to investigate the effects of Cyr61 on COX-2 expression in chorioretinal vascular endothelial (RF/6A) cells and to study the possible signal transduction pathway and the transcriptional mechanisms.

Materials and methods: The effects of Cyr61 on COX-2 expression were evaluated via determining the mRNA, protein, and prostaglandin (PG) E2 levels of RF/6A cells. To examine the pathway in this process, RF/6A cells were pretreated with integrin ανβ3-blocking antibodies, a FAK inhibitor (PF573228), a PI3K inhibitor (LY294002), and an Akt inhibitor (A6730), respectively. Electrophoretic mobility shift assays (EMSAs) and luciferase reporter assays were applied to assess if NF-κB was involved in this response.

Results: Cyr61 stimulated the expression of COX-2 at the mRNA, protein, and PGE2 levels in a dose-dependent and time-dependent manner. Both COX-2 and PGE₂ levels were attenuated during the response to Cyr61 stimulation by pretreatment with integrin ανβ3-blocking antibodies, PF573228, LY294002, and A6730 respectively. EMSA revealed that all of the aforementioned inhibitors suppressed NF-κB activation. Luciferase reporter assays further indicated that the mutation of the NF-κB-binding element in the COX-2 gene promoter reduced its gene expression.

Conclusions: Induction of COX-2 by Cyr61 is mediated through the activation of the integrin ανβ3, FAK, PI3K/Akt, and NF-κB pathways in RF/6A cells.

Uveal melanoma, the most common primary intraocular malignancy in adults, presents significant therapeutic challenges. With the advancement of surgical instruments and techniques, exoresection (ab-externo) and endoresection (ab-interno) have emerged as viable treatment methods. These surgical interventions can be implemented particularly for tumors exceeding traditional size criteria for plaque brachytherapy and for tumors that are too large, which pose an elevated risk of radiation-related complications. Moreover, surgical interventions not only enhance the potential for functional vision preservation and globe retention but also provide effective control of intraocular tumors and metastatic disease when combined with adjunctive radiation therapy. Exoresection, an external approach, involves dissection and removal of the tumor through a scleral flap, while endoresection utilizes vitreoretinal surgical techniques for internal tumor excision. Both surgical techniques for uveal melanoma removal are highly challenging, carry significant risks of complications, and should be performed by experienced vitreoretinal surgeons specializing in ocular oncology at specialized centers. They aim to preserve the eye and potentially maintain useful vision while saving patients' lives, a crucial consideration in ocular oncology. These surgical modalities have become increasingly relevant as the field progresses towards more conservative, function-preserving approaches in cancer treatment. The aim of this article is to conduct a comparative analysis of exoresection and endoresection in the context of uveal melanoma management. By critically evaluating these surgical modalities, this review seeks to provide clinicians with valuable insights to guide treatment decisions for patients with large uveal melanomas.

Indeterminate choroidal melanocytic tumors may exhibit growth under observation, but the clinical significance of early versus late growth remains unclear. In this review we aim to explore the temporal profile of growth to detect benign and malignant subsets. There was no specific set of tumor dimensions or characteristics applied for exclusion or inclusion except that all included tumors had to be described as indeterminate or suspicious nevus and observed for growth by the authors. Nine published studies (1977-2021) that included 8766 patients were reviewed. The primary outcomes were time to event (growth) and its correlation with the growth rate of small choroidal melanoma. The studies were largely retrospective and had differing inclusion criteria: largest basal diameter of 7.5-24 mm (mean, 14.83 mm) and maximum height of 2-6.7 mm (mean, 4.19 mm). Most defined growth by a change in height of >0.3 mm or base of >0.5. Among 8606 tumors followed, 478 (5.6%) showed growth over 5 years, with growth rates in individual studies ranging from 2% to 55% (mean: 19.0%). The highest event rate occurred in the 1st year (range: 0.7%-15%; mean: 6.5%), stabilizing to 0%-5% (mean: 1.5%) by year 5. The majority (range: 52%-83%; mean: 67%) were observed to grow in the initial 2 years (early growth). Over subsequent years (late growth), the proportion of growing tumors reduced and stabilized by years 4 and 5 to a mean of 6.1% and 8.3%, respectively. Time-to-event analysis indicates the heterogeneity of IMTs. Tumors growing in the first 2 years (early growth) may be melanoma in the evolution and their characteristics previously identified as the risk factors for growth may be interpreted as the factors predictive or diagnostic of small choroidal melanoma. In contrast, tumors demonstrating growth in subsequent years (late growth), after documented stability, may represent malignant transformation of a choroidal nevus.

Purpose: Intravitreal injections (IVIs) have been the most important treatment strategies in retinal diseases. With the increasing use of IVIs, the incidence of endophthalmitis has inevitably risen. Triamcinolone acetonide (TA) used in IVIs has been suspected as a risk factor for post-IVI endophthalmitis. This study investigates the incidence, clinical presentations, and microscopic findings of post-IVI endophthalmitis with or without TA, aiming to provide a better understanding of this issue.

Materials and methods: This retrospective study included patients receiving IVIs at a tertiary referral center from September 2010 to August 2020. Injections were performed under sterile conditions, and endophthalmitis was diagnosed based on acute ocular symptoms within 6 weeks postinjection. Statistical analysis was preformed between endophthalmitis with or without TA.

Results: Out of 18,365 IVIs, the incidence of endophthalmitis was 0.038%. The incidence of TA-associated endophthalmitis (TAAE) (5 in 939 IVIs, 0.532%) was significantly higher (P < 0.0001) than that of non-TAAE (2 in 17,426 IVIs, 0.011%). All five TAAE cases were culture negative, while the two non-TAAE cases were culture positive with Staphylococcus epidermidis (P < 0.0001). The outcomes for TAAE were generally good, with patients returning to their preendophthalmitis vision levels. Risk factors for TAAE included prior IVIs and prior TA injections. Microscopy revealed fern-like crystalline materials in the anterior chamber of one TAAE case.

Conclusion: This study highlights that TA is significantly associated with a higher incidence of post-IVI endophthalmitis, which is also significantly associated with culture-negative results. This implies the possibility of a noninfectious cause in TAAE.

To summarize the characteristics of the retinal detachments (RDs) that are associated with choroidal colobomas that occur in pediatric and adult patients. A choroidal coloboma is a rare disorder that results from an incomplete closure of the embryonic optic fissure, and their size can range from small colobomas with isolated chorioretinal involvement to large colobomas affecting the iris, choroid, retina, and optic nerve. A RD is occasionally associated with choroidal colobomas, and histological studies of the area of the choroidal coloboma show an absence of normal choroidal tissue, retinal pigment epithelium (RPE), and retina. Near the margin of the coloboma, the inner retinal layer has a central continuation of the marginal intercalary membrane (ICM) within the coloboma. The outer layer folds back, becomes disorganized, and fuses with the RPE. The inner retina gradually thins and merges with the marginal ICM with a high incidence of tears of the ICM developing along the edge of the coloboma or toward the center. Because of the high association of the causative retinal breaks being located within the colobomatous area, vitrectomy, endolaser photocoagulation around the margin of coloboma, and long-term tamponade with silicone oil or gas are recommended treatments. In addition, the presence of the macula within the area of the laser photocoagulation should be considered. However, the recurrence rate is high and multiple surgeries are required to reattach the detached retina.

A 54-year-old female was referred because of a pigmented iris lesion with uncontrolled glaucoma in the left eye. The intraocular pressure (IOP) was 54 mm Hg despite anti-glaucoma medications. Her visual acuity (VA) was 20/100. A slit-lamp examination showed corneal edema and a darkly pigmented small iridociliary lesion (Ultrasound biomicroscopy: 5 mm × 3 mm × 2 mm) with diffuse pigment shedding onto the anterior iris surface and diffuse circumferential pigmentation of the trabecular meshwork with wide-open angle (gonioscopy). Diagnostic fine needle aspiration biopsy of the main tumor and anterior chamber lavage were performed. Cytology revealed polygonal cells with dense intracytoplasmic pigment obscuring nuclear details diagnostic of a melanocytoma. During follow-up, as the tumor continued to cause new pigment shedding with high IOP, therefore, excision of the primary tumor via iridocyclectomy was performed. At postoperative 1 month, the IOP was 13 mm Hg with maximal medical therapy for glaucoma requiring glaucoma shunt surgery. At 6 months, the IOP remained below 13 mm Hg and the VA was 20/50 without recurrence of pigment shedding. Necrotic iris melanocytoma, though rare, can lead to pigment dispersion glaucoma. Surgical excision of the primary tumor, coupled with glaucoma surgery, proved effective in controlling intraocular pressure and preserving vision in this case.