Psychological interventions to reduce intraocular pressure (IOP) in glaucoma patients: a review.

PURPOSE: Glaucoma has been increasing recognised to cause significant mental health burden to patients while psychological factors also play important roles in the development and progression of glaucoma. This review presents the current evidence of the impact of psychological interventions in glaucoma patients to improve their holistic care in terms of both physical and mental health by modulating psychological symptoms and supporting glaucoma control. METHODS: A literature search was conducted on PubMed for relevant studies up to February 2022. Types of psychological interventions include meditation, autogenic relaxation, music, hypnosis, motivational interviewing, psychological nursing and bright light exposure. Outcomes investigated were ocular parameters including intraocular pressure, mental health, patient motivation and satisfaction, and overall quality of life. RESULTS: Seventeen studies investigating the effects of psychological interventions on improving the care of glaucoma patients were reviewed. Daily meditation for 30 to 60 min has been shown to be effective in improving glaucoma control in terms of reducing intraocular pressure by 1.5 to 6.1 mmHg and improving ocular perfusion and quality of life. The impacts of music, autogenic training and psychological nursing on glaucoma control, vision outcomes and psychological symptoms are also promising while bright light exposure has shown some effects on sleeping quality. However, there is insufficient basis to support the adoption of motivational interviewing or hypnosis in glaucoma patients yet. CONCLUSION: Psychological interventions, especially meditation, can play a bigger role in the holistic care of glaucoma patients by controlling disease progression as an adjunct to conventional approaches and alleviating the mental health burden caused by the disease through stress reduction and emotional regulation. They empower patients to gain greater control of their disease and provides additional advantages of low cost, non-invasiveness and minimal side effects. Future research should involve well-conducted randomised trials with larger sample sizes and longer duration of intervention and follow-up to establish the long-term benefits for glaucoma patients.

OCTA biomarkers in adults aged 50 and above: a prospective and cross-sectional community-based study.

BACKGROUND/AIMS: To assess the normative values and parameters of optical coherence tomography angiography (OCTA) influencing the best corrected visual acuity (BCVA) in adults aged 50 and above. METHODS: This was a prospective cross-sectional study from an eye screening programme in Hong Kong for 4188 citizens aged 50 and above. Images were analysed using a validated quantification software calculating vessel density and capillary perfusion density (CPD), along with other OCTA parameters, such as the foveal avascular zone area (FAZ) and circularity. OCTA data was collected from May 2019 to December 2020, including a total of 4188 healthy eyes from 4188 subjects. RESULTS: Mean superficial vessel density (MSVD) was 14.48 ± 3.60 mm- 1, while the mean capillary perfusion density (MCPD) was 0.41 ± 0.06. Multivariate analysis revealed ageing (ß = 0.321, p < 0.001), being male (ß=-0.089, p < 0.001), having a high body mass index (BMI) (ß = 0.039, p = 0.006), high FAZ area and low FAZ circularity (ß = 0.039 and - 0.034, p = 0.01 and 0.024 respectively), low MSVD in the outer ring (ß=-0.513, p < 0.001), specifically in the nasal and temporal outer quadrants (ß = -0.226 and - 0.259, p < 0.001 for both), and low MCPD in the outer superior quadrant (ß= -0.123, p = 0.016) being independently associated with BCVA. CONCLUSION: High FAZ area and low FAZ circularity, low MSVD in the outer ring, specifically the nasal and temporal outer quadrants, and low MCPD in the outer superior quadrant can be used as biomarkers in predicting a low visual acuity in adults aged 50 and above.

Randomized Control Trial of the Impact of Patient Decision Aid Developed for Chinese Primary Open-Angle Glaucoma Patients.

INTRODUCTION: Patient decision aid (PDA) is a tool to prompt shared decision-making. The aim of this study was to evaluate the impact of a PDA on Chinese primary open-angle glaucoma patients. METHODS: All subjects were randomized into control and PDA group. The questionnaires, including 1) glaucoma knowledge; 2) 8-item Morisky medication adherence scale (MMAS-8); 3) 10-item glaucoma medication adherence self-efficacy scale (GMASES-10); and 4) 16-item decision conflict scale (DCS), were evaluated at baseline, 3- and 6-month follow-up. RESULTS: Totally, 156 subjects participated in this study, including 77 in the control group and 79 in the PDA group. Compared to the control group, PDA group showed around 1 point more improvement in disease knowledge at both 3 and 6 months (both p < 0.05), 2.5 (95% CI: [1.0, 4.1]) and 1.9 (95% CI: [0.2, 3.7]) points more improvement in GMASES-10 at 3 and 6 months, respectively, and reduction in DCS by 8.8 (95% CI: [4.6, 12.9]) points more at 3 months and 13.5 (95% CI: [8.9, 18.0]) points more at 6 months. No difference was detected in MMAS-8. CONCLUSION: PDA led to improvement in disease knowledge and self-confidence in medication adherence and reduced decision conflict compared to control group for at least 6 months.

Patient-centred care in ophthalmology: current practices, effectiveness and challenges.

PURPOSE: To summarise different patient-centred care approaches that can be used in ophthalmology and review their effectiveness. METHODS: An Entrez Pubmed search on publications concerning different patient-centred care was performed on September 7, 2021. Articles on animal research, non-English language and review articles were excluded after manually screening by two authors. RESULTS: A total of 16 articles were reviewed after curation by the authors for relevance. Patient-centred care has advantages in improving disease knowledge, enhancing doctor-patient communications and improving mental well-being of patients. Various methods including intensive patient education, patient-centred communication techniques during consultations, personal disease records, education programme for caregivers, on-site ocular care for residential care home resident and shared medical appointments can be used to enhance patient-centred care. CONCLUSIONS: Current strategies in patient-centred care in ophthalmology were found to be useful. However, they have not been widely practised and more studies would be required generate an evidence-based recommendation for future use.

Sociodemographic, behavioral, and medical risk factors associated with visual impairment among older adults: a community-based pilot survey in Southern District of Hong Kong.

BACKGROUND: The last visual survey of older adults in Hong Kong was a district-level study in 2002, with no assessment of behavioral and medical risk factors for visual impairment (VI). Our objectives were to determine the latest VI prevalence among older adults, significance of any spatial and temporal differences on the prevalence, and any associations of sociodemographic, behavioral and medical risk factors with VI from a multi-perspective analysis. METHODS: Community-based pilot survey of residents from a suburb of Hong Kong, aged ≥50, using a standardized questionnaire, was conducted in 2016. RESULTS: Of the 222 subjects, crude rates of bilateral and unilateral VI were 9.46 and 32.88%, respectively, or corresponding age-and-gender-adjusted rates of 6.89 and 30.5%. Older age and lower educational were associated with higher risk for unilateral VI, while older age, temporary housing, obesity and hyperlipidemia were associated with higher risk for bilateral VI. Smoking and alcohol-drinking status were not associated with unilateral or bilateral VI. Relative changes in ORs of hypertension or educational level on unilateral or bilateral VI were >  10% after adjusting for age. Interaction term between hyperlipidemia and gender or obesity was significant for unilateral VI. Gender, hypertension and cataract were not associated with unilateral or bilateral VI in general population of pooled analysis but were identified as risk factors in specific subgroups of stratified analysis. Refractive error (myopia or hyperopia) was significantly associated with VI in the eye-level analysis after adjusting the inter-eye correlation. CONCLUSIONS: Sociodemographic and medical risk factors contributed to VI, but behavioral risk factors did not. Sociodemographic disparities of visual health existed. Age was the confounders of the VI-hypertension or VI-educational level relationships. Gender and obesity were more likely to have multiplicative effect on unilateral VI when combined with hyperlipidemia. Stratified analysis should be conducted to provide further insight into the risk factors for VI in specific populations. Uncorrected refractive error remains a significant cause of impaired vision. The spatial and temporal differences in bilateral VI prevalence from the previous local study indicates a territory-wide survey is needed to assess regional differences and overall prevalence of VI in Hong Kong.

Lacrimal sac bacteriology and susceptibility pattern in infants with congenital nasolacrimal duct obstruction in the 1st year of life: a cross-sectional study.

BACKGROUND: Congenital nasolacrimal duct obstruction (CNLDO) is one of the main causes of epiphora in infants, and antibiotics are usually used as a conservative therapy in the first year. Yet, little is known about the bacteriology of the occluded lacrimal drainage system in this group of patients. The aim of this study was to evaluate the microbiology of lacrimal sac (LS) in Chinese children with CNLDO in their first year of life. METHODS: Patients with CNLDO between May 1, 2017 and August 31, 2018 at a tertiary care children's hospital were enrolled. The study recruited infants who received lacrimal probing under 1 year old, and refluxed discharge from LS was collected. Samples were cultured and susceptibility test was performed for positive culture. RESULTS: Thirty-two patients with CNLDO were included. The ratio of male to female was 23:9. The mean age was 6.7 ± 2.4 (1.7-12) months. Positive cultures was identified in 87.5% of the sample, and presented 38 strains of bacteria. Mixed infection was identified in 10 (31.3%) children. Gram-positive bacteria accounted for 60.5% of all the strains, with Streptococcus (50%) being the most frequent species, whereas Haemophilus (21.1%) and Neisseriae (13.2%) were most common isolates for Gram-negative organisms. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 2 infants whose symptoms resolved by a routine probing. No difference of bacteriology pattern was detected between patients under 6 months old and those beyond. The pathogens were highly sensitive to chloramphenicol (88%) and levofloxacin (84%), but resistant to erythromycin (40%) and sulfamethoxazole (32%). CONCLUSIONS: Infants with CNLDO under 1 year of age presented predominance of Streptococcus as Gram-positive organism, and Haemophilus as Gram-negative organism. Levofloxacin was an active topical antibiotic agent with few chance of resistance especially for Chinese children. These findings could help clinicians choose optimal medicine for CNLDO as the conservative treatments.

One-year results of 0.01% atropine with orthokeratology (AOK) study: a randomised clinical trial.

PURPOSE: To report the 1-year results of an investigation into whether there is an additive effect between 0.01% atropine and orthokeratology (ortho-k), in a single-masked, two-arm, randomised controlled trial: Combined Atropine with Orthokeratology (AOK) for myopia control study (ClinicalTrials.gov number: NCT02955927). METHODS: Chinese children aged between 6 and 11 years with 1.00-4.00 D of myopia, astigmatism <2.50 D, and no more than 1.00 D anisometropia, were randomly assigned either to an AOK group or ortho-k only (OK) group at a 1:1 ratio. Subjects in the AOK group instilled one drop of 0.01% atropine into each eye, 10 min before nightly wear of ortho-k lenses. The primary outcome, axial elongation, was examined at 6-monthly intervals, along with secondary outcomes including best-corrected visual acuity (BCVA), manifest refraction, accommodation, pupil size, and corneal topography. RESULTS: 29 AOK and 30 OK subjects completed the 1-year visit. The overall axial elongation rate was significantly slower in the AOK group than in the OK group (mean (S.D.), 0.07 (0.16) mm vs 0.16 (0.15) mm, respectively; p = 0.03). A significant between-group difference in axial elongation was observed over the first 6-month period only (p < 0.001), but not over the second period (p = 0.818). At the 1-year visit, increases in mean (S.D.) mesopic and photopic pupil sizes in the AOK group were 0.64 (0.48) mm and 0.36 (0.34) mm, respectively, which were significantly higher than 0.10 (0.50) mm and 0.02 (0.28) mm in the OK group (p < 0.001). At the 6-month visit, a significant moderate negative correlation was found between axial elongation and the increase in photopic pupil size (r = -0.42, p = 0.02) in the AOK group. CONCLUSIONS: There is an additive effect between 0.01% atropine and ortho-k over one year, with mean axial elongation in the AOK group 0.09 mm slower than that in the OK group. It appears that the additive effect was only during the first six months; a second-year investigation is warranted to determine whether the effect is sustained over time.

Mucolipidosis Type II Affecting 1 Fetus and Placental Disk of a Dichorionic-Diamnionic Twin Gestation: A Case Report and Review of the Literature.

Mucolipidosis type II, also known as I-cell disease, is an autosomal recessive inborn error of metabolism, resulting from loss-of-function mutations in GNPTAB. Affected infants exhibit multiple physical anomalies and developmental delay, and death from disease follows in early childhood. Here we present an instructive case of mucolipidosis type II affecting 1 fetus and placental disk in a dichorionic-diamnionic twin pregnancy delivered at 36-wk gestation. The second twin and placental disk showed no abnormality. On microscopic examination, the affected placenta displayed marked vacuolization of the syncytiotrophoblast and Hofbauer cells, which was confirmed on ultrastructural examination. To our knowledge, this is the first description of placental findings in a twin pregnancy, wherein only 1 twin is affected by an inborn error of metabolism. This provides an opportunity to highlight the placental abnormalities seen in this group of diseases, and to emphasize the role of pathologic examination in early detection of otherwise unsuspected inborn errors of metabolism.

Prospective study on a novel treatment for leaking cystic bleb: Efficacy and safety of collagen crosslinking.

IMPORTANCE: Management of cystic bleb leak is difficult. It would be essential to look for a method to strengthen the original pathological conjunctiva and reverse bleb leak. BACKGROUND: To evaluate the long-term efficacy and safety of collagen crosslinking in patients with leaking cystic bleb. DESIGN: Prospective interventional case series at a university-based hospital. PARTICIPANTS: Twelve eyes in 12 subjects with late-onset bleb leak from cystic bleb, without indications for prompt surgical interventions were included. METHODS: The subjects underwent crosslinking with 0.1% riboflavin application to bleb surface, followed by ultraviolet irradiation for 30 minutes. The subjects were followed up at baseline and at 1 week, 1 month, 3 months, 6 months post-treatment and then every 6 months afterwards. MAIN OUTCOME MEASURES: Interval from treatment to cessation of bleb leak, recurrence rate of bleb leak and side effects of treatment. RESULTS: The mean follow-up after crosslinking was 29.33 ± 12.45 months. Bleb leak subsided in 11 (92%) of 12 patients after a single session of crosslinking, after 1 to 8 weeks (median 3 weeks). Time to leak cessation was significantly correlated with the number of prior glaucoma interventions (R = .71, P = .014). Bleb wall at 3 months was significantly thicker than at baseline (0.70 ± 0.67 vs 0.81 ± 0.62 mm, P = .008). None of the patients experienced any complications. CONCLUSIONS AND RELEVANCE: Crosslinking achieves resolution of cystic bleb leak which lasts for at least 12 months, without the need of subsequent surgical interventions. Crosslinking is a simple, non-invasive treatment for bleb leak. It aims to restore the integrity of conjunctiva.

Early intraocular pressure change after peripheral iridotomy with ultralow fluence pattern scanning laser and Nd:YAG laser in primary angle-closure suspect: Kowloon East Pattern Scanning Laser Study Report No. 3.

PURPOSE: Our purpose was to assess the early intraocular pressure (IOP) changes of ultralow fluence laser iridotomy using pattern scanning laser followed by neodymium:yttrium-aluminum-gamet (Nd:YAG) laser. METHODS: This is a prospective interventional study. Thirty-three eyes of 33 adult Chinese primary angle-closure suspect subjects were recruited for prophylactic laser peripheral iridotomy. Sequential laser peripheral iridotomy was performed using pattern scanning laser followed by Nd:YAG laser. Visual acuity (VA) and IOP were measured before treatment, at 1 h, 1 day, 1 week, 1 month, 3 months and 6 months after laser. Laser energy used and complications were documented. Corneal endothelial cell count was examined at baseline and 6 months. Patency of the iridotomy was assessed at each follow-up visit. RESULTS: All subjects achieved patent iridotomy in a single session. The mean energy used was 0.335+/-0.088 J for the pattern scanning laser, and 4.767+/-5.780 mJ for the Nd:YAG laser. The total mean energy was 0.339+/-0.089 J. None of the eyes developed a clinically significant IOP spike (≥ 8 mmHg) at 1 h and 1 day after laser use. Only four eyes developed higher IOP at 1 h and all were ≤3 mmHg compared to baseline. The mean IOP was 13.8+/-2.5 mmHg at 1 h and 11.5+/-2.2 mmHg at 1 day, both were significantly lower than baseline (15.8+/-2.1 mmHg) (P < 0.001). Mean VA (logMAR) was similar at 1 h post laser compared to baseline (0.23 vs 0.26). There was also no statistically significant difference in mean VA at other follow-up visits compared to baseline. Peripheral iridotomy closure was encountered in two (6.1%) eyes, one at 1 month and another at 6 months follow-up. There were no complications including hyphema, peripheral anterior synechia formation nor prolonged inflammation throughout the follow-up period. There was no significant loss in corneal endothelial cell counts at 6 months (2255+/-490) compared to baseline (2303+/-386) (P = 0.347). CONCLUSIONS: Sequential LPI using an ultralow fluence pattern scanning laser, followed by a Nd:YAG laser, is safe and efficacious, and produces no IOP spike in dark irides of primary angle-closure suspects. Further studies to investigate its role in the treatment of other angle-closure conditions are warranted.

Effects of Riboflavin and Ultraviolet Illumination on the Biomechanical Properties of Conjunctiva.

PURPOSE: Our experiment evaluated the biomechanical effects of riboflavin and ultraviolet A illumination, in terms of covalent bonding, permeability, and indentation rupture force, on excised cattle conjunctiva. MATERIALS AND METHODS: Cattle conjunctiva was extracted and divided into the treatment group, which was soaked in riboflavin, followed by ultraviolet light illumination, and the control group. Samples were subsequently analysed on a Fourier transform infrared spectrum test to identify the presence of amide bonds, a permeability test to assess the diffusion of methylene blue across conjunctiva, and an indentation rupture force test. RESULTS: The Fourier transform infrared spectrum test showed a significantly increased amide I band after treatment (p = 0.043), as well as in amide II, amide A, and amide B bands. The permeability test showed a reduced permeability to methylene blue after treatment (n = 25) compared to the control (n = 24; p = 0.03). The indentation rupture test showed a higher maximal rupture force in the treated samples (n = 10; p = 0.07). CONCLUSIONS: The study suggested that riboflavin and ultraviolet A illumination (commercially available as collagen crosslinking) strengthened cattle conjunctiva by increasing its amount of covalent bonds, reducing its permeability, and possibly improving its resistance to rupture. This is the first study in the collagen crosslinking literature on the biomechanical properties of conjunctival tissue.

Clinical characteristics of optic neuritis in Hong Kong population: 10-year review.

PURPOSE: To review the clinical course of adult patients with acute optic neuritis over 10 years in Hong Kong, and the results were compared with other studies among Asian and Caucasian patients. METHODS: This study retrospectively analysed the clinical features of 38 adult patients (51 eyes) presented with optic neuritis in a Hong Kong hospital over 10 years (2001-2010). RESULTS: Optic neuritis had a female predominance (68%). The mean age of presentation was 40 years old. Disc swelling (39%) was more common compared to the optic neuritis treatment trial (ONTT). The recovery time ranged from no recovery to 5 years, with a mean of 6.0 months. However, vision continued to deteriorate despite initial improvement in 45% of patients. Only 11.8% of the eyes attained final visual acuity (VA) of 1.0 or better, while 31.4% had VA 0.1 or worse. Multiple sclerosis or neuromyelitis optica only occurred in 10.4% of patients. Three of our patients who did not receive any treatment showed faster recovery than the average. CONCLUSIONS: Optic neuritis in Hong Kong is mostly a clinically isolated syndrome. Our patients presented at a later age and showed a worse visual outcome. Corticosteroid according to ONTT protocol remained our mainstay of treatment although it did not benefit our patients as much as ONTT study. More work on the long-term prognosis and treatment strategies is worthwhile among Chinese optic neuritis patients.

A cross-sectional comparative study on chronic ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series.

PURPOSE: To compare the chronic ocular manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis patients from a 15-year cohort. METHODS: All SJS and TEN patients admitted to our burn intensive care unit between 1999 and 2014 were invited for assessment. Slit-lamp examination was performed, and ocular condition was graded according to the Sotozono scoring System, which depended on the extent of cornea, conjunctiva and lid involvement. Tear osmolarity was also measured. RESULTS: A total of 18 SJS and 4 TEN cases with an average of 92 and 135 months from disease onset were included. The average age of onset was 46.4 ± 16.6 in SJS and 43.5 ± 19.3 in TEN patients. The LogMAR visual acuity was 0.209 ± 0.591 in SJS and 0.489 ± 0.688 in TEN patients (p = 0.048). The average total Sotozono score was 3.75 ± 7.32 in SJS and 6.88 ± 9.49 in TEN (p = 0.358). Neither the age of onset (p = 0.787), length of follow-up (p = 0.256) nor disease type (SJS vs TEN, p = 0.188) predicted the Sotozono score. There was a statistically significant correlation between Sotozono score and LogMAR VA (r s = 0.437, p = 0.003). CONCLUSION: The average total Sotozono score was higher in the TEN group than in the SJS group, but the difference was not statistically significant. Nevertheless, the score correlated with the visual acuity which was statistically worse in the TEN group.

High prevalence of MiTF staining in undifferentiated pleomorphic sarcoma: caution in the use of melanocytic markers in sarcoma.

AIMS: The diagnosis of undifferentiated pleomorphic sarcoma (UPS) may be challenging, as other lesions with undifferentiated spindle cell morphology must be excluded, including melanoma. Microphthalmia-associated transcription factor (MiTF) stains naevi and epithelioid melanomas, as well as some mesenchymal neoplasms. The aim of this study was to evaluate the prevalence of MiTF and melanocytic markers in UPS and a subset of atypical fibroxanthoma (AFX). METHODS AND RESULTS: MiTF, SOX10, Melan-A, HMB45 and S100 immunostaining was performed on resection specimens from 19 UPSs and five AFXs. Next-generation sequencing of 50 genes was performed in UPSs to exclude dedifferentiated melanoma. In 17 of 19 UPSs (89%), tumour cells showed nuclear positivity for MiTF that was not eliminated by casein block. Three showed focal nuclear staining for HMB45, which was eliminated by casein block. One showed focal nuclear vacuole staining for S100 with red but not brown chromogen. None expressed SOX10 or Melan-A. Mutational analysis of 15 UPSs with adequate DNA showed no mutations within hotspot regions of BRAF, KIT, or NRAS. Four of five AFXs (80%) stained with MiTF; other markers were negative. CONCLUSION: There is a high prevalence of nuclear MiTF expression in UPSs (89%) and AFXs (80%). Rare UPSs showed non-specific nuclear HMB45 or S100 staining. These findings argue against using MiTF in isolation to differentiate between UPS or AFX and melanoma, and caution in interpreting focal staining for a single additional melanocytic marker. Casein block may eliminate non-specific staining. MiTF should be used to support a diagnosis of melanoma only if multiple melanocytic markers are positive.

Collagen crosslinking in the management of leaking cystic blebs: a prospective study.

PURPOSE: To evaluate the effectiveness and safety of collagen crosslinking for leaking cystic blebs. METHODS: A prospective study was conducted on subjects with cystic bleb leaks without indications for urgent surgical intervention. Collagen crosslinking with riboflavin 0.1 % and ultraviolet A irradiation for 30 min was applied to the cystic bleb surface in five patients. Subjects were followed up for at least 20 weeks (mean: 35.5 ± 11.5 weeks) to monitor the length of time to the cessation of bleb leak, as well as visual acuity, intraocular pressure, and the presence of adverse effects arising from the treatment. RESULTS: Results showed that a single session of collagen crosslinking was effective in stopping cystic bleb leak. In two of the five subjects, the bleb leak subsided 1 week post-treatment, in one patient after 2 weeks, and in the two more complicated cases, after 4 weeks. This effect was maintained for a mean period of 33.5 ± 10.2 weeks after bleb leak cessation. Treatment was effective even in patients with friable conjunctiva following multiple surgical interventions and severe leak, although a longer period was needed for resolution of the bleb leak. The intraocular pressure and visual acuity were largely stable before and after treatment. No side effects or complications arose from this treatment. CONCLUSIONS: We recommend a trial of collagen crosslinking on leaking cystic blebs without indications for immediate surgical interventions. It is a relatively easy, non-invasive, pain-free, and potential repeatable procedure for treating leaking cystic blebs, with the aim of strengthening the underlying pathological conjunctiva.

Recurrent acute angle-closure attack due to plateau iris syndrome after cataract extraction with or without argon laser peripheral iridoplasty: a case report.

BACKGROUND: We describe two cases of recurrent acute angle-closure attack in patients with plateau iris syndrome after cataract extraction. Argon laser peripheral iridoplasty and cataract extraction have been used to reduce the occurrence of acute angle-closure attack in plateau iris syndrome although the risk cannot be completely eliminated. There is no consensus on the long term management of plateau iris syndrome. This is, as far as we know, the first case report of recurrent acute angle-closure attack in plateau iris syndrome after cataract extraction. CASE PRESENTATION: We report two cases of recurrent acute angle-closure attack in 2 Chinese patients with plateau iris syndrome. The first patient was a 69 year-old woman who received bilateral argon laser peripheral iridoplasty and cataract extraction 2 years prior to the latest acute angle-closure with right eye intraocular pressure 48 mmHg. The attack was aborted medically. Peripheral iridotomy was patent and argon laser peripheral iridoplasty marks were mostly at peripheral 2/3 of the iris. Anterior segment optical coherence tomography confirmed bilateral plateau iris configuration. Use of long term pilocarpine or repeated argon laser peripheral iridoplasty to prevent recurrent angle-closure attack was discussed but she opted for observation. The second patient was a 64 year-old man presented with acute angle-closure after cataract extraction despite placement of laser peripheral iridotomy. Plateau iris syndrome was confirmed by anterior segment optical coherence tomography and he received argon laser peripheral iridoplasty. CONCLUSIONS: Acute angle-closure due to plateau iris syndrome can still occur despite previous cataract extraction and argon laser peripheral iridoplasty. These are the first reported cases of recurrent acute angle-closure attack due to plateau iris syndrome following cataract extraction, with or without previous argon laser peripheral iridoplasty. Repeated treatment with argon laser peripheral iridoplasty or pilocarpine could be considered although the long term efficacy is questionable. Argon laser peripheral iridoplasty should be applied as peripheral as possible so as to open up the drainage angle effectively.

Chromophobe Renal Cell Carcinoma with Sarcomatoid Differentiation: Clinicopathologic Correlation and Molecular Findings.

Introduction: Sarcomatoid differentiation has been reported in approximately 8% of chromophobe renal cell carcinoma (RCC) and is associated with a worse prognosis. We aim to describe the clinicopathologic and molecular findings of chromophobe RCC with sarcomatoid differentiation. Methods: Surgical pathology database was searched to identify chromophobe RCC with sarcomatoid differentiation from January 2015 to December 2021. Results: Five patients were diagnosed with chromophobe RCC with sarcomatoid differentiation. The median age at the time of diagnosis was 57 years (range 51-61 years). Three patients died after median follow-up of 12.1 months (range 1.6-18.2 months). The median tumor size was 10.7 cm (range 5.6-13.6 cm). The median percentage of sarcomatoid component was 60% (range 10-90%), and the median percentage of necrosis was 30% (range 10-50%). One tumor demonstrated osteoid formation. PAX8, keratin 7, KIT (CD117), and Hale colloidal iron were positive in the epithelial component, whereas the sarcomatoid component was positive for vimentin, CD10, and high Ki67 proliferative index. Molecular testing was performed in three specimens: all were TP53 mutated and microsatellite stable. One aggressive tumor had RB1 frameshift mutation and copy number gains for TERT and CUL4A. Conclusion: Chromophobe RCC with sarcomatoid differentiation is a rare entity with aggressive behavior. Percentage of sarcomatoid component, necrosis, and the occurrence of metastasis is associated with worse prognosis. Molecular profiling reveals frequent TP53 mutation. While TERT promoter mutation has no prognostic implication, FLCN inactivation may be associated with a less aggressive course. The clinical significance of RB1 loss is unclear.

What's new in genitourinary pathology 2023: WHO 5th edition updates for urinary tract, prostate, testis, and penis.

The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduced many significant changes relevant to urologic daily practice, mainly to renal tumors which was covered in the What's New newsletter in September 2022. In this newsletter, we summarize the notable changes to bladder, prostate, testis, and penis based on the 5th edition of the WHO.

Spatial comparison of molecular features associated with resistance to pembrolizumab in BCG unresponsive bladder cancer.

Intravenous immune checkpoint inhibition achieves a 40% 3-month response in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ. Yet, only half of the early responders will continue to be disease-free by 12 months, and resistance mechanisms are poorly defined. We performed spatial profiling of BCG-unresponsive tumors from patients responsive or resistant to intravenous pembrolizumab treatment, analyzing samples both before initiating and 3 months post-intravenous pembrolizumab treatment. We analyzed 119 regions of interest, which included 59 pairs of epithelial and adjacent stromal segments across five patients: two responders and three non-responders. We demonstrate that BCG unresponsive tumors with an inflamed PanCK+ tumor area and an infiltrated stromal segment respond better to intravenous pembrolizumab. Furthermore, using segment-specific gene signatures generated from a cohort of BCG unresponsive NMIBC treated with intravesical BCG+pembrolizumab, we find that non-inflamed, immune-cold tumors that do not respond to intravenous pembrolizumab exhibit a favorable outcome to the combined application of BCG and pembrolizumab. For the first time, we have identified molecular features of tumors associated with response and resistance to intravenous pembrolizumab in BCG unresponsive NMIBCs. Further research with more patients and alternative checkpoint inhibitors is essential to validate our findings. We anticipate that using a transcriptomics signature like the one described here can help identify tumors with a higher possibility of responding to intravenous pembrolizumab.

Supernatant fluid from endobronchial ultrasound-guided transbronchial needle aspiration for rapid next-generation sequencing.

INTRODUCTION: There is an increasing demand to optimize the workflow and maximize tissue available for next-generation sequencing (NGS) for non-small cell carcinoma. We looked at transbronchial needle endobronchial ultrasound-guided bronchoscopy with transbronchial needle aspiration samples and evaluated the performance of supernatant (SN) fluid processed from a dedicated aspirate collected for NGS testing. MATERIALS AND METHODS: Nineteen samples were collected and processed using a new workflow. Five aspirates were collected in formalin. One additional dedicated pass was collected fresh and centrifuged. The resulting cell pellet was added to formalin for cell block (CB) processing. DNA and RNA were extracted from concentrated SN for targeted testing using the Oncomine Precision Assay (Thermo Scientific, Waltham, MA). NGS results from the corresponding CB samples were used as "controls" for comparison. RESULTS: Thirty-one mutations were detected in SN (Table 1). The most frequently mutated genes were TP53 (35%), EGFR (23%), KRAS (13%), CTNNB1 (6%), and ERBB2 (6%). There was 100% concordance between the mutations detected in SN and corresponding CBs with comparable variant allele frequencies. Turnaround time of NGS results was 1 day for SN compared to 4-10 days for CB. CONCLUSIONS: We were able to demonstrate the usefulness of SN for reliable rapid molecular results. We successfully incorporated the workflow for tissue handling and processing among our clinical, cytopathology, and molecular teams. Molecular results were available at the same time as the cytologic diagnosis, allowing for timely reporting of a comprehensive diagnosis. This approach is particularly useful in patients with advanced disease requiring urgent management.