PI3K/AKT/mTOR pathway-derived risk score exhibits correlation with immune infiltration in uveal melanoma patients.

Uveal melanoma (UVM) is a rare but highly aggressive intraocular tumor with a poor prognosis and limited therapeutic options. Recent studies have implicated the PI3K/AKT/mTOR pathway in the pathogenesis and progression of UVM. Here, we aimed to explore the potential mechanism of PI3K/AKT/mTOR pathway-related genes (PRGs) in UVM and develop a novel prognostic-related risk model. Using unsupervised clustering on 14 PRGs profiles, we identified three distinct subtypes with varying immune characteristics. Subtype A demonstrated the worst overall survival and showed higher expression of human leukocyte antigen, immune checkpoints, and immune cell infiltration. Further enrichment analysis revealed that subtype A mainly functioned in inflammatory response, apoptosis, angiogenesis, and the PI3K/AKT/mTOR signaling pathway. Differential analysis between different subtypes identified 56 differentially expressed genes (DEGs), with the major enrichment pathway of these DEGs associated with PI3K/AKT/mTOR. Based on these DEGs, we developed a consensus machine learning-derived signature (RSF model) that exhibited the best power for predicting prognosis among 76 algorithm combinations. The novel signature demonstrated excellent robustness and predictive ability for the overall survival of patients. Moreover, we observed that patients classified by risk scores had distinguishable immune status and mutation. In conclusion, our study identified a consensus machine learning-derived signature as a potential biomarker for prognostic prediction in UVM patients. Our findings suggest that this signature is correlated with tumor immune infiltration and may serve as a valuable tool for personalized therapy in the clinical setting.

Clinical Analysis of Macular Choroidal Thickness in Pseudoexfoliative Glaucoma and Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the differences in macular choroidal thickness and volume among patients with pseudoexfoliative glaucoma (PXG), patients with primary open-angle glaucoma (POAG), and controls. METHODS: A total of 50 PXG patients (50 eyes) and 56 POAG patients (56 eyes) were selected as the PXG group and the POAG group, respectively, in this case-control study. A total of 54 age-, gender-, IOP-, and axial length-matched healthy individuals (54 eyes) were selected as the control group. Enhanced-depth imaging-optical coherence tomography (EDI-OCT) was used to measure and analyze the choroidal thicknesses and volumes in 9 macular regions of all subjects. RESULTS: The choroidal thicknesses in the central subfield (CSM), temporal inner macula (TIM), inferior inner macula (IIM), and temporal outer macula (TOM) and the mean macular choroidal thickness were significantly thinner in the PXG group than in the control group (all P < 0.05). The choroidal volumes in the TIM, IIM, and TOM and the mean macular choroidal volume were significantly smaller in the PXG group than in the control group (all P < 0.05). The choroidal thicknesses in the CSM and IIM and the mean macular choroidal thickness were significantly thinner in the PXG group than in the POAG group (all P < 0.05). The choroidal volumes in the IIM and TOM and the mean macular choroidal volume were significantly smaller in the PXG group than in the POAG group (all P < 0.05). Multivariable linear regression analysis showed that the mean macular choroidal thickness was significantly thinner in association with older subjects and longer axial length eyes. There was no association between the macular choroidal thickness of various macular regions and visual field mean defect (MD) in groups PXG and POAG (all P > 0.05). CONCLUSIONS: The macular choroidal thicknesses and volumes (inferior and temporal) in PXG patients were thinner and smaller than those in POAG patients and healthy individuals. The role of choroidal thickness changes in the course of PXG remains unclear. A future prospective study is needed to better define these changes in PXG patients.

Microcatheter-Assisted Trabeculotomy Combined With Deep Sclerectomy and Trabeculectomy in Young to Middle-Aged Adults With Advanced Primary Open-Angle Glaucoma: 1-Year Result.

Objective: We aimed to evaluate the safety and clinical efficacy of ab externo microcatheter-assisted trabeculotomy combined with deep sclerectomy and trabeculectomy (MATT-DS-Trab) in the surgical management of advanced primary open-angle glaucoma (POAG). Methods: According to the inclusion criteria, we retrospectively collected and analyzed 37 POAG cases in advanced stage who received MATT-DS-Trab. The intraocular pressure (IOP), best corrected visual acuity (BCVA), use of anti-glaucoma drugs, shape of the filtering bleb, size of the scleral lake, complications, and the surgical success rate were recorded. Results: The mean IOP was 37.50 ± 8.11 mmHg before the operation, while it depleted to 10.08 ± 2.01 and 11.43 ± 2.07 mmHg at 1 week and 12 months after the operation, respectively (both P < 0.001 compared to preoperative IOP). From none to two kinds of anti-glaucoma drugs were used 12 months after surgery on the patients, which were significantly reduced compared with that preoperatively (P < 0.001). An L-type filtering bleb was the main form at all time points after the operation. At 12 months following surgery, an F-type filtering bleb accounted for 5.41% and no E-type filtering bleb was recorded. The length and height of the scleral lake shrunk with time, but there was no statistical significance (P > 0.05). Also, there was no correlation between the size of the scleral pool and the IOP (P > 0.05). At 12 months after the operation, the complete success rates were 94.59, 83.78, and 72.97% according to standards A (≤18 mmHg), B (≤15 mmHg), and C (≤12 mmHg), respectively. Intraoperative complications were mainly anterior chamber hemorrhage, and no complications related to the filtration bleb were observed after the operation. Conclusion: Based on multichannel mechanisms, MATT-DS-Trab is able to effectively reduce IOP in advanced POAG patients, with few serious complications and a high success rate.

Clinical observation of macular choroidal thickness in primary chronic angle-closure glaucoma.

PURPOSE: To comparatively analyze differences in macular choroidal thickness and volume in primary chronic angle-closure glaucoma (PACG) eyes. METHODS: Thirty-one PACG patients were sequentially selected for this case-control study. Thirty-one eyes with PACG were included in group A, 31 fellow eyes were included in group B, and group C included 67 normal eyes. Enhanced-depth imaging optical coherence tomography (EDI-OCT) was used to measure choroidal thickness and volume. RESULTS: The choroidal thicknesses and volumes of the central subfield macula (CSM), nasal inner macula (NIM), temporal inner macula (TIM), inferior inner macula (IIM), temporal outer macula (TOM), inferior outer macula (IOM), and mean macula (MM) in group A were all higher than those in group C (P < 0.05). The choroidal thicknesses and volumes of the NIM, superior inner macula (SIM), IIM, nasal outer macula (NOM), and MM in group B were all higher than those in group C (P < 0.05). No statistically significant differences were found between groups A and B (P > 0.05). The choroidal thicknesses of different macular regions in group A were not correlated with the mean defect (MD). CONCLUSION: Increased macular choroidal thickness may be a common anatomical characteristic of PACD eyes. Macular choroidal thickness is not a good marker for assessing PACG severity.

CO2 Laser-Assisted Deep Sclerectomy Surgery Compared with Trabeculectomy in Primary Open-Angle Glaucoma: Two-Year Results.

PURPOSE: To compare the effectiveness and safety of carbon dioxide (CO2) laser-assisted deep sclerectomy surgery (CLASS) and trabeculectomy (Trab) for treatment of primary open-angle glaucoma (POAG). METHODS: In this retrospective and comparative study, 77 eyes of 62 patients with POAG were studied and divided into the CLASS and Trab groups. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of medications, surgical success rate, and complications were analyzed. RESULTS: The mean follow-up periods were 27.89 ± 2.94 months and 26.11 ± 2.06 months in the CLASS and Trab groups, respectively. 30 eyes (24 patients) underwent CLASS and 47 eyes (38 patients) underwent Trab. The BCVA in the CLASS and Trab groups was recovered to baseline at postoperative 1 week and 1 month, respectively. At last follow-up visits, a remarkable reduction in the IOP and number of medications was observed in both groups, and no significant difference was found in those between the two groups. The complete success rates were 51.7% and 47.7% in postoperative 24 months in the CLASS and Trab groups, respectively (P > 0.05). There were higher rates of delayed anterior chamber formation (21.3%) and thin-wall filtrating blebs (10.6%) in the Trab group. Meanwhile, the peripheral anterior synechiae were only observed in the CLASS group, and the ratio was 30%. CONCLUSIONS: CLASS is an effective and safe treatment modality for POAG, with fewer filtering bleb-related complications and quicker visual recovery in the early postoperative stage than trabeculectomy. The efficacy of lowering intraocular pressure was similar for both procedures.

Analysis of bleb morphology after CLASS with ultrasound biomicroscopy and clinical grading scale.

OBJECTIVE: Filtration in the area subjected to CO2 laser-assisted sclerectomy surgery (CLASS) is described using ultrasound biomicroscopy (UBM) and the clinical grading scale to evaluate the mechanism of intraocular pressure (IOP) reduction. METHODS: Twenty-eight patients with open-angle glaucoma underwent CLASS. The Indiana Bleb Appearance Grading Scale evaluation was performed 1 month after surgery to determine bleb height, extent, vascularity, and leakage. UBM was used to describe and measure the surgical area. Bleb morphology, the size of the scleral lake, scleral route, and trabeculodescemetic membrane (TDM) thickness were examined. RESULTS: One month after CLASS, IOP significantly decreased from 20.46 ± 3.92 mmHg to 12.71 ± 2.99 mmHg, and the anterior chamber depth significantly more shallow, from 2.75 ± 0.36 mm to 2.61 ± 0.33 mm(p < 0.05). Shallow uplift occurred in 71.43% of the blebs, and 64.29% of the blebs were within 1 to 2 h; 82.15% showed mild or moderate vascular hyperemia, and the Seidel test was negative. UBM showed that all eyes had an intact TDM, with a mean thickness of 99.3 ± 22.2 µm; 21 eyes (75%) had L-type (low reflective). The scleral lake anteroposterior length, height, and transversal length were 2.247 ± 1.831 mm, 0.520 ± 0.234 mm, and 3.312 ± 0.423 mm, respectively. The TDM thickness and postoperative IOP were positively correlated, and the size of the scleral lake was not correlated with IOP reduction. Four eyes (14.29%) exhibited cyclodialysis. CONCLUSION: UBM examination indicated the aqueous humor drainage route. In the early stage after CLASS, subconjunctival and choroidal drainage routes might be the major mechanism underlying IOP reduction. Mild and moderate congestion of bleb blood vessels warrant attention to avoid early bleb scarring.

Surgical site characteristics after CLASS followed by ultrasound biomicroscopy and clinical grading scale: a 2-year follow-up.

OBJECTIVE: This study describes the imaging of the filtering area in CO2 laser-assisted sclerectomy surgery (CLASS) using ultrasound biomicroscopy (UBM) combined with the Indiana Bleb Appearance Grading Scale (IBAGS) and evaluates the mechanism by which CLASS lowers the intraocular pressure (IOP). METHODS: Twenty-eight cases (28 eyes) of primary open-angle glaucoma that could not be controlled by drugs underwent CLASS. At 1, 3, 6, 12, 18, and 24 months after surgery, IBAGS was used to evaluate the external morphology of the filtering blebs, and UBM was used to describe and measure their internal structure. RESULTS: During the early period after CLASS, most cases showed diffuse filtering blebs with a serious degree of congestion. At the end of follow-up, most cases did not present filtering blebs. All patients showed an intact and thin trabeculodescemetic membrane (TDM) with an average thickness of 0.094 ± 0.017 mm. The scleral reservoir size gradually decreased over time and tended to stabilize after 18 months. At 3 and 6 months after surgery, 53.57% of the patients had abnormalities in the TDM area, and after laser goniopuncture treatment, the scleral reservoir became slightly larger and the IOP decreased. The TDM thickness was not correlated with postoperative IOP, and the scleral reservoir size was negatively correlated with IOP. CONCLUSION: During the early phase after CLASS, the subconjunctival and suprachoroidal pathways may be the main mechanisms lowering IOP; over time, internal drainage pathways such as the intrascleral, trabecular-meshwork, and suprachoroidal pathways play greater roles in lowering IOP.

Analysis of Peripapillary and Macular Choroidal Thickness in Eyes with Pseudoexfoliative Glaucoma and Fellow Eyes.

PURPOSE: To compare differences in peripapillary and macular choroidal thickness in pseudoexfoliative glaucoma (PXG) eyes, nonexfoliative fellow eyes, and normal eyes. METHODS: This case-control study included 37 PXG patients (group A: 37 PXG eyes; group B: 37 nonexfoliative fellow eyes) and 37 sex-, age-, and axial length-matched healthy volunteer eyes (group C). Peripapillary and macular choroidal thickness and volume were measured in all subjects via enhanced-depth imaging-optical coherence tomography. RESULTS: The average peripapillary (AP) choroidal thickness was (130.10 ± 46.14) µm, (131.43 ± 46.00) µm, and (147.89 ± 53.32) µm; average macular (AM) choroidal thickness was (191.72 ± 68.07) µm, (204.62 ± 69.54) µm, and (215.10 ± 45.40) µm; and average volume was (0.59 ± 0.21) µm3, (0.63 ± 0.21) µm3, and (0.65 ± 0.14) µm3 in groups A, B, and C, respectively. NIP choroidal thickness was significantly lower in groups A and B than in group C (P < 0.05). TIM and TOM choroidal thickness and volume were significantly lower in group A than in group C (P < 0.05). NIM, SIM, NOM, IOM, AM choroidal thickness and volume, and CSM choroidal thickness were significantly lower in group A than in group B (P < 0.05). CSM, TIM, and TOM in group A and TIM, TOM choroidal thickness, and volume in group B were significantly lower than in group C (P < 0.05). CONCLUSIONS: NIP choroidal thickness in PXG eyes and nonexfoliative fellow eyes and temporal macular choroidal thickness in PXG eyes were significantly lower than in normal eyes. Macular choroidal thickness (except in temporal regions) was significantly lower in PXG eyes than in nonexfoliative fellow eyes. Changes in peripapillary and macula choroidal thickness further elucidate the choroid's role in PXG development and progression.

The Effects of Trabeculectomy on Pseudoexfoliation Glaucoma and Primary Open-Angle Glaucoma.

PURPOSE: To compare long-term effects of trabeculectomy on pseudoexfoliation glaucoma (PXG) and primary open-angle glaucoma (POAG). METHODS: This retrospective case-control study included 53 eyes of PXG and 76 eyes of POAG. Intraocular pressure (IOP), number of antiglaucoma medications used, surgical success rate, and occurrence of complications were observed and statistically analyzed in both groups at 3 and 6 months and at 1, 3, and 5 years after trabeculectomy. Surgical success was defined according to the following 3 criteria: (1) IOP ≤ 21 mmHg; (2) IOP ≤ 18 mmHg; (3) IOP ≤ 15 mmHg. Complete success is defined as patients met these criteria without medical treatment, and qualified success is defined as patients met these criteria with medical treatment (≤3 medications). Cumulative probabilities of success were compared using the Kaplan-Meier survival analysis. RESULTS: For the 3 criteria, there were no statistically significant differences in complete and qualified success rates between the two groups at 3 and 6 months after trabeculectomy (P > 0.05). For criterion A, complete success rates in PXG at 3 and 5 years after surgery were lower than those in POAG; for criterion B, complete and qualified success rates in PXG at 3 and 5 years after surgery were lower than those in POAG; for criterion C, complete and qualified success rates in PXG at 1, 3, and 5 years after surgery were lower than those in POAG, the differences were statistically significant (P < 0.05). CONCLUSIONS: The short-term success rates of both types of glaucoma were similar; however, the long-term success rate of PXG was significantly lower, and it was difficult to achieve long-term control of IOP at a low target level.

Comparison of Macular Choroidal Thickness and Volume between Pseudoexfoliative Glaucoma and Pseudoexfoliative Syndrome.

PURPOSE: To evaluate the difference in macular choroidal thickness and volume between patients with pseudoexfoliative glaucoma (PXG), patients with pseudoexfoliative syndrome (PEX), and normal controls. METHODS: This case-control study included 49 PXG patients (group A), 33 PEX patients (group B), and 42 sex-, age-, and axial length-matched healthy volunteer eyes (group C). The macular choroidal thickness and volume of all subjects studied were measured by enhanced depth imaging optical coherence tomography. RESULTS: The average macular (AM) choroidal thickness was 170.79 ± 50.18 µm, 184.65 ± 57.54 µm, and 206.46 ± 48.90 µm, and the average volume was 0.52 ± 0.15 µm3, 0.56 ± 0.17 µm3, and 0.63 ± 0.15 µm3 in groups A, B, and C, respectively. The macular choroidal thickness, the volumes of various macular regions, and the average choroidal thickness and volume in group A were lower than those in group C (all P < 0.05). There were no significant differences in the macular choroidal thickness, volumes of various macular regions, or average choroidal thickness or volume between group A and B (all P > 0.05). The macular choroidal thickness and volume of the TIM and SOM in group B were lower than those in group C (P < 0.05). There was no association between the macular choroidal thickness of various macular regions and visual field mean defect (MD) in group A (all P > 0.05). CONCLUSION: The macular choroidal thickness in patients with PXG or PEX (TIM and SOM) is thinner than that in normal subjects. The macular choroidal thickness in patients with PXG is not significantly different from that in patients with PEX. The role of macular choroidal thickness changes in the glaucomatous damage of patients with PXG is still unclear.

Digital evaluation of orbital development in chinese children with congenital microphthalmia.

PURPOSE: To evaluate the asymmetry of bilateral orbital development in Chinese children with congenital microphthalmia and to provide a criterion for tailoring treatment timing and therapy. DESIGN: Retrospective cohort study. METHODS: By combining multisection helical computerized tomography imaging with a computer-aided design system, we measured 38 children between 0 and 6 years of age with congenital microphthalmia and 70 normal children of the same age group. Variables were measured, including orbital volume, depth, width, and height and eyeball volume. Displacement of the orbital rims was calculated by mirroring the unaffected orbit across the midsagittal plane of body. RESULTS: Significant differences were observed between the orbital volume, eyeball volume, orbital width, and orbital height of the affected and unaffected sides of children with congenital microphthalmia (P < .001). The difference between the orbital depth of the affected and unaffected sides was not significant (P = .055). Growth of the inferior and lateral rims retarded by an average of 3 mm, whereas that of the medial and superior rims retarded by less than 1 mm. CONCLUSIONS: The amount of decrease in orbital volume of children with congenital microphthalmia is related to the severity of the disease (decrease in size of the eye), rather than to age. Retarded orbital development is evident primarily in the inferior and lateral rims, correlating mostly with zygomatic and then maxilla and frontal bone. The growth of the affected orbit slows down or even stagnates by 3 years of age. Intervention therapy before 3 years of age was critical.