Interim Analysis of Clinical Outcomes with Open versus Closed Conjunctival Implantation of the XEN45 Gel Stent.

OBJECTIVE: To examine the longitudinal postoperative outcomes of open versus closed conjunctiva implantation of the XEN45 gel stent. DESIGN: Retrospective multicenter study. SUBJECTS: One hundred ninety-three patients with glaucoma underwent XEN45 implantation via an open or closed conjunctiva approach. METHODS: Data on patient demographics; diagnoses; preoperative and postoperative clinical data; outcome measures, including intraocular pressure (IOP); use of glaucoma medications; visual acuity; and complications were collected. Statistical analyses were performed with P < 0.05 as significant. MAIN OUTCOME MEASURES: Failure was defined as < 20% reduction in IOP from the medicated baseline or a IOP of > 21 mmHg at 2 consecutive visits at postoperative month 1 and beyond, the need for subsequent operative intervention or additional glaucoma surgery, or a catastrophic event, such as loss of light perception. Eyes that had not failed by these criteria and were not on glaucoma medications were considered complete successes. Overall success was defined as those who achieved success either with or without topical medications. RESULTS: Patients were followed for an average of 17 months. Complete success was achieved in 42.5% and 24.7% of the open and closed groups, respectively (P = 0.01). Overall success was achieved in 64.2% and 37.0% of the open and closed groups, respectively (P < 0.001) at the last follow-up. Bleb needling was performed in 12.4% of eyes in the open group compared with 40% of eyes in the closed group. An IOP spike of ≥ 10 mmHg was twice as likely to occur in the closed group compared with the open group during the postoperative period (40% vs. 18%; P = 0.001). CONCLUSIONS: Implantation of XEN45 with opening of the conjunctiva resulted in a lower IOP with greater success and lower needling rate compared with those achieved with the closed conjunctiva technique. Similar rates of postoperative complications and vision loss were noted in each group. Although both procedures provide substantial IOP reduction, the open technique appears to result in higher success rates and fewer postoperative interventions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Extreme intraocular pressure and steroid-dependent iritis.

A 50-year-old ophthalmic technician was referred by her retina specialist for urgent consultation due to markedly elevated intraocular pressure (IOP) unresponsive to medical therapy. Her history included chronic polyarticular juvenile rheumatoid arthritis and chronic uveitis requiring ongoing topical steroid therapy. She had a sub-Tenon injection of Kenalog (triamcinolone) 18 months prior to referral. Chronic topical anti-inflammatory therapy included nepafenac (Ilevro) and prednisolone acetate 2 times a day. Attempts to discontinue topical steroid resulted in worsening inflammation. The patient was referred when the IOP measured 44 mm Hg in the left eye despite aggressive medical therapy, including acetazolamide. The IOP improved slightly when loteprednol was substituted for prednisolone acetate. Current medications in the left eye include brimonidine 3 times a day, loteprednol 2 times a day, nepafenac 2 times a day, and fixed combination latanoprost + netarsudil at bedtime. Her only medication in the right eye was travoprost. She is intolerant to dorzolamide. She was also taking acetazolamide 500 mg 2 times a day. She was not taking any anticoagulants. Past surgical history included cataract surgery in each eye. She has not had laser trabeculoplasty in either eye. Examination revealed uncorrected visual acuity of J1+ in the right eye (near) and 20/30 in the left eye (mini-monovision). There was no afferent pupillary defect. There was mild band keratopathy in each eye while the central cornea was clear in both eyes without keratic precipitates. Here angles were open to gonioscopy without peripheral anterior synechia. There was mild to moderate flare in each eye with trace cells. The IOP was 17 mm Hg in the right eye and 31 mm Hg in the left. Central corneal thickness measured 560 µm and 559 µm in the right and left eye respectively. There was a well-positioned intraocular lens within each capsule with a patent posterior capsulotomy. There was mild vitreous syneresis but no vitreous cell. The cup to disc ratio was 0.5 in each eye with a symmetrical neural rim. The retina was flat without macular edema. Visual field was normal in both eyes (Figures 1 and 2). Optical coherence tomography of retinal nerve fiber layer (RNFL) is shown in Figure 3 and retinal ganglion cell layer is shown in Supplemental Figure 1 (http://links.lww.com/JRS/A756).JOURNAL/jcrs/04.03/02158034-202301000-00020/figure1/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure2/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure3/v/2022-12-26T045736Z/r/image-tiff Please comment on your management of this patient's left eye.

Diagnostic Yield and Complication Rate of Stereotactic Biopsies in Precision Medicine of Gliomas.

Background: An integrated diagnosis consisting of histology and molecular markers is the basis of the current WHO classification system of gliomas. In patients with suspected newly diagnosed or recurrent glioma, stereotactic biopsy is an alternative in cases in which microsurgical resection is deemed to not be safely feasible or indicated. In this retrospective study, we aimed to analyze both the diagnostic yield and the safety of a standardized biopsy technique. Material and Methods: The institutional database was screened for frame-based biopsy procedures (January 2016 until March 2021). Only patients with a suspected diagnosis of glioma based on imaging were included. All tumors were classified according to the current WHO grading system. The clinical parameters, procedural complications, histology, and molecular signature of the tissues obtained were assessed. Results: Between January 2016 and March 2021, 1,214 patients underwent a stereotactic biopsy: 617 (50.8%) for a newly diagnosed lesion and 597 (49.2%) for a suspected recurrence. The median age was 56.9 years (range 5 months-94.4 years). Magnetic resonance imaging (MRI)-guidance was used in 99.3% of cases and additional positron emission tomography (PET)-guidance in 34.3% of cases. In total, stereotactic serial biopsy provided an integrated diagnosis in 96.3% of all procedures. The most frequent diagnoses were isocitrate dehydrogenase (IDH) wildtype glioblastoma (n = 596; 49.2%), oligodendroglioma grade 2 (n = 109; 9%), astrocytoma grade 3 (n = 108; 8.9%), oligodendroglioma grade 3 (n = 76; 6.3%), and astrocytoma grade 2 (n = 66; 5.4%). A detailed determination was successful for IDH 1/2 mutation in 99.4% of cases, for 1p/19q codeletion in 97.4% of cases, for TERT mutation in 98.9% of cases, and for MGMT promoter methylation in 99.1% of cases. Next-generation sequencing was evaluable in 64/67 (95.5%) of cases and DNA methylome analysis in 41/44 (93.2%) of cases. Thirteen (1.1%) cases showed glial tumors that could not be further specified. Seventy-three tumors were different non-glioma entities, e.g., of infectious or inflammatory nature. Seventy-five out of 597 suspected recurrences turned out to be post-therapeutic changes only. The rate of post-procedural complications with clinical symptoms of the Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher was 1.2% in overall patients and 2.6% in the subgroup of brainstem biopsies. There was no fatal outcome in the entire series. Conclusion: Image-guided stereotactic serial biopsy enables obtaining reliable histopathological and molecular diagnoses with a very low complication rate even in tumors with critical localization. Thus, in patients not undergoing microsurgical resection, this is a valuable tool for precision medicine of patients with glioma.

The value of stereotactic biopsy of primary and recurrent brain metastases in the era of precision medicine.

Background: Brain metastases (BM) represent the most frequent intracranial tumors with increasing incidence. Many primary tumors are currently treated in protocols that incorporate targeted therapies either upfront or for progressive metastatic disease. Hence, molecular markers are gaining increasing importance in the diagnostic framework of BM. In cases with diagnostic uncertainty, both in newly diagnosed or recurrent BM, stereotactic biopsy serves as an alternative to microsurgical resection particularly whenever resection is not deemed to be safe or feasible. This retrospective study aimed to analyze both diagnostic yield and safety of an image-guided frame based stereotactic biopsy technique (STX). Material and methods: Our institutional neurosurgical data base was searched for any surgical procedure for suspected brain metastases between January 2016 and March 2021. Of these, only patients with STX were included. Clinical parameters, procedural complications, and tissue histology and concomitant molecular signature were assessed. Results: Overall, 467 patients were identified including 234 (50%) with STX. Median age at biopsy was 64 years (range 29 - 87 years). MRI was used for frame-based trajectory planning in every case with additional PET-guidance in 38 cases (16%). In total, serial tumor probes provided a definite diagnosis in 230 procedures (98%). In 4 cases (1.7%), the pathological tissue did not allow a definitive neuropathological diagnosis. 24 cases had to be excluded due to non-metastatic histology, leaving 206 cases for further analyses. 114 patients (49%) exhibited newly diagnosed BM, while 46 patients (20%) displayed progressive BM. Pseudoprogression was seen in 46 patients, a median of 12 months after prior therapy. Pseudoprogression was always confirmed by clinical course. Metastatic tissue was found most frequently from lung cancer (40%), followed by breast cancer (9%), and malignant melanoma (7%). Other entities included gastrointestinal cancer, squamous cell cancer, renal cell carcinoma, and thyroid cancer, respectively. In 9 cases (4%), the tumor origin could not be identified (cancer of unknown primary). Molecular genetic analyses were successful in 137 out of 144 analyzed cases (95%). Additional next-generation sequencing revealed conclusive results in 12/18 (67%) cases. Relevant peri-procedural complications were observed in 5 cases (2.4%), which were all transient. No permanent morbidity or mortality was noted. Conclusion: In patients with BM, frame-based stereotactic biopsy constitutes a safe procedure with a high diagnostic yield. Importantly, this extended to discerning pseudoprogression from tumor relapse after prior therapy. Thus, comprehensive molecular characterization based on minimal-invasive stereotactic biopsies lays the foundation for precision medicine approaches in the treatment of primary and recurrent BM.

Immune checkpoint inhibitor associated ocular hypertension (from presumed trabeculitis).

PURPOSE: Immune checkpoint inhibitors (ICIs) are associated with a range of immune-related adverse ophthalmic events. To date, there are scant reports of ocular hypertension coupled with ICI-associated uveitis. However, in instances of ocular hypertension in the context of only mild uveitic reaction and absence of synechiae, trabeculitis is considered. This series describes our observations of presumed trabeculitis in the setting of ICI therapy and investigates the clinical findings, treatment and outcome of these patients. OBSERVATIONS: Two eyes of 2 patients (both male aged 65 and 43) developed a mild anterior uveitis and elevated intraocular pressure (IOP) with open angles and no evidence of peripheral anterior synechiae in association with ICI treatment for their malignancy; and were considered to have presumed unilateral trabeculitis. The patients underwent 10 cycles (6.53 months) and 2 cycles (3.33 months) respectively of ICI therapy before developing ophthalmic symptoms. Neither patient was on systemic or topical steroid treatment at time of diagnosis and there was no suspicion of a viral etiology for the inflammation. Following management, the anterior uveitis resolved and IOP rapidly returned to normal in both eyes: ICI therapy was discontinued in both patients (and uneventfully re-challenged at a lower dose in one patient) and both eyes were treated with a combination of topical and/or oral glaucoma medications and topical steroids. CONCLUSIONS AND IMPORTANCE: Uveitic ocular hypertension has been described with ICI. However, another immune-related mechanism for ocular hypertension with unique clinical characteristics, includes trabeculitis. We describe two cases of trabeculitis in the setting of ICI-therapy. The intraocular inflammation and elevated intraocular pressure which characterizes trabeculitis often responds rapidly to conservative treatment. In both patients checkpoint inhibitor therapy was discontinued and, in one patient, was re-challenged at a lower dose without recurrence. Immunotherapy is now more widely used for cancer treatment and its potential ocular manifestations should be shared with the ophthalmic community.

Comparison of Clinical Outcomes with Open Versus Closed Conjunctiva Implantation of the XEN45 Gel Stent.

PURPOSE: To describe the efficacy and safety of open versus closed conjunctival implantation of the XEN45 Gel Stent (Allergan Inc). DESIGN: Retrospective, multicenter study. PARTICIPANTS: A total of 137 patients with glaucoma who underwent XEN45 implantation via open or closed conjunctival methods. The XEN45 was implanted as a stand-alone procedure or at the time of cataract surgery by 5 surgeons. METHODS: Patient demographics, diagnoses, preoperative and postoperative clinical data, outcome measures including intraocular pressure (IOP), use of glaucoma medications, visual acuity, and complications were collected. Statistical analyses were performed with P < 0.05 as significant. MAIN OUTCOME MEASURES: Failure was defined as less than 20% reduction of IOP from medicated baseline or IOP >21 mmHg at 2 consecutive visits at postoperative month 1 and beyond, the need for subsequent operative intervention or additional glaucoma surgery, or a catastrophic event such as loss of light perception. Eyes that had not failed by these criteria and were not on glaucoma medications were considered complete successes. Eyes that had not failed but required glaucoma medications were defined as qualified successes. RESULTS: Complete success was achieved in 31% and 56% of the closed and open groups, respectively (P = 0.01). Qualified success was achieved in 53% and 71% of the closed and open groups, respectively (P = 0.06). At postoperative month 12, the open conjunctiva group was using fewer glaucoma medications than the closed group (0.9 vs. 1.8, respectively; P = 0.02). At postoperative month 12, the open group had a significantly greater percentage of IOP reduction compared with the closed group (43.1% vs. 24.8%, respectively; P = 0.02). Postoperative needling rates were higher in the closed group compared with the open group (36.1% vs. 11.8%, P = 0.001). CONCLUSIONS: Implantation of the XEN45 with opening of the conjunctiva is a safe and efficacious procedure to lower IOP with comparable success rate and lower needling rate compared with the closed conjunctiva technique. Prospective evaluation of the various methods for XEN45 implantation will allow for further comparison.

Subconjunctival microinvasive glaucoma surgeries: an update on the Xen gel stent and the PreserFlo MicroShunt.

PURPOSE OF REVIEW: This review will provide an update on surgical techniques, outcomes, and complications for two new translimbal bleb-forming surgical glaucoma devices. RECENT FINDINGS: The XEN Gel Microstent and PreserFlo MicroShunt comprise a category of subconjunctival microinvasive glaucoma surgery developed with the aim of improving the predictability and safety profile of bleb-forming procedures. Both devices are made of noninflammatory material which limits postsurgical inflammation and scarring and have a valve-less intrinsic flow-limiting design, which decreases the risk of hypotony. There are various techniques of implantation for the XEN Gel Microstent each with their own advantages and disadvantages. SUMMARY: These devices have demonstrated promising outcomes in early experimental literature with similar intraocular pressure-lowering effects to traditional incisional surgery such as trabeculectomy or tube shunt surgery, but with fewer risks. Future randomized, prospective studies should be done to compare these gel stents and microshunts both to each other and to other traditional glaucoma surgeries.

Subluxated cataract lens surgery using sutured segments or rings and implantation of toric intraocular lenses.

PURPOSE: To evaluate the intraoperative performance and postoperative outcomes of toric intraocular lens (IOL) with suture ring implantation in adult patients with subluxated lenses. SETTING: Department of Ophthalmology, Kaiser Permanente, Santa Clara, California, and the Eye Institute of Utah, Salt Lake City, Utah, USA. DESIGN: Retrospective case review. METHODS: Eyes with subluxated cataractous lenses and preoperative corneal astigmatism having toric IOL implantation with a sutured ring or segment were studied. Preoperative and postoperative analyses included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and cylindrical power postoperatively and 3, 6, and 12 months postoperatively. RESULTS: Twenty-one eyes of 15 patients were studied. The median follow-up was 14.6 months. The mean CDVA at the final follow-up (0.10 logMAR ± 0.15 [SD]) was significantly improved from the mean preoperative CDVA (0.73 ± 0.40 logMAR). Postoperative cylindrical power was significantly improved in all patients (mean reduction in astigmatism 2.37 ± 1.46 diopters). Patients who required postoperative enhancement had anterior laser capsulotomy for bilateral capsule phimosis (2 eyes), photorefractive keratectomy (1 eye), pupilloplasty (1 eye), and posterior laser capsulotomy (2 eyes). CONCLUSION: Cataract removal and implantation of a toric IOL combined with a sutured ring or segment capsule stabilizing device was a safe and efficacious long-term solution for patients with subluxated cataract lenses and corneal astigmatism.

A Widening Gap? Changes in Multiple Lifestyle Risk Behaviours by Socioeconomic Status in New South Wales, Australia, 2002-2012.

BACKGROUND: Socioeconomic inequalities in health outcomes have increased over the past few decades in some countries. However, the trends in inequalities related to multiple health risk behaviours have been infrequently reported. In this study, we examined the trends in individual health risk behaviours and a summary lifestyle risk index in New South Wales, Australia, and whether the absolute and relative inequalities in risk behaviours by socioeconomic positions have changed over time. METHODS: Using data from the annual New South Wales Adult Population Health Survey during the period of 2002-2012, we examined four individual risk behaviours (smoking, higher than recommended alcohol consumption, insufficient fruit and vegetable intake, and insufficient physical activity) and a combined lifestyle risk indicator. Socioeconomic inequalities were assessed based on educational attainment and postal area-level index of relative socio-economic disadvantage (IRSD), and were presented as prevalence difference for absolute inequalities and prevalence ratio for relative inequalities. Trend tests and survey logistic regression models examined whether the degree of absolute and relative inequalities between the most and least disadvantaged subgroups have changed over time. RESULTS: The prevalence of all individual risk behaviours and the summary lifestyle risk indicator declined from 2002 to 2012. Particularly, the prevalence of physical inactivity and smoking decreased from 52.6% and 22% in 2002 to 43.8% and 17.1% in 2012 (p for trend<0.001). However, a significant trend was observed for increasing absolute and relative inequalities in smoking, insufficient fruit and vegetable consumption, and the summary lifestyle risk indicator. CONCLUSIONS: The overall improvement in health behaviours in New South Wales, Australia, co-occurred with a widening socioeconomic gap. IMPLICATIONS: Governments should address health inequalities through risk factor surveillance and combined strategies of population-wide and targeted interventions.

UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells.

It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbour a branched mitochondrial network with oxidative phosphorylation as the main energy source. A role for mitochondria in hPSC bioenergetics and in cell differentiation therefore remains uncertain. Here, we show that hPSCs have functional respiratory complexes that are able to consume O(2) at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis and ATP is consumed by the F(1)F(0) ATP synthase to partially maintain hPSC mitochondrial membrane potential and cell viability. Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential.