Open-angle glaucoma and Fuchs dystrophy.

A 62-year-old woman with a history of moderate myopia, long-standing open-angle glaucoma (OAG), and Fuchs dystrophy in both eyes was referred for consultative care. She had prior trabeculectomy in 1984 and 1992 in the left and right eyes, respectively. She is 3 months post-Descemet-stripping endothelial keratoplasty (DSEK) in the left eye, now referred with uncontrolled intraocular pressure (IOP) despite maximum tolerated medical therapy. Current medical therapy for IOP consists of acetazolamide 250 mg by mouth 2 times a day, brimonidine 2 times a day in the left eye, dorzolamide 2 times a day in the left eye, and timolol 2 times a day in the left eye. The patient has a history of presumed steroid response; however, her corneal surgeon has requested that the steroid be continued for the next several months because of the recent DSEK. The IOP in the left eye has ranged from the mid-20s to mid-30s since DSEK. The right eye has consistently had pressure in the low teens and below for many years without topical antihypertensive medications. Examination revealed stable visual acuity at 20/30 and 20/40 in the right and left eyes, respectively, IOP was 12 mm Hg in the right eye and 25 mm Hg in the left eye by Goldman applanation, irregular but reactive pupils without afferent defect, and full confrontational visual fields. Slitlamp examination showed superior low avascular bleb, moderate-to-severe guttae, and posterior chamber IOL in the right eye. The left eye showed superior low diffuse bleb, clear DSEK graft, quiet chamber, superonasal iridectomy, and posterior chamber IOL with an open posterior capsule. The conjunctiva was moderately scarred but a repeat trabeculectomy or Xen Gel stent (Abbvie) appeared possible. The angles were wide open in each eye. Fundus examination was normal aside from myopic, anomalous-appearing nerves with an approximate cup-to-disc ratio of 0.90 in both eyes. Humphrey visual field showed nonspecific changes on the right and moderate nasal defect on the left eye, stable to previous examinations dating back to 2018 (Figure 1JOURNAL/jcrs/04.03/02158034-202407000-00018/figure1/v/2024-07-10T174240Z/r/image-tiff and Figure 2JOURNAL/jcrs/04.03/02158034-202407000-00018/figure2/v/2024-07-10T174240Z/r/image-tiff). Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) revealed moderated thinning in both eyes that was also stable to prior examinations (Figure 3JOURNAL/jcrs/04.03/02158034-202407000-00018/figure3/v/2024-07-10T174240Z/r/image-tiff). Her axial length measured 25.23 and 26.34 mm in the right and left eyes, respectively. Central corneal thickness was 553 µm in the right eye and 563 µm in the left eye before her DSEK procedure. What would be your approach to management of this patient's left eye, addressing the following: Rationale for your procedure of choice? Would you over-rule the corneal surgeon and stop the steroid in an attempt to obviate the need for glaucoma surgery? Does the age of onset of glaucoma affect your surgical decision making? Note that patient age at the time of trabeculectomy was 22 years. Are some procedures better suited for patients after DSEK surgery?

Managing primary open-angle glaucoma in the setting of suboptimal surgical outcomes in the fellow eye.

A 62-year-old woman with mild myopia presented to her local optometrist for a routine examination and was found to have intraocular pressure (IOP) of 30 mm Hg in both eyes and cupped nerves. She had a family history of glaucoma in her father. She was started on latanoprost in both eyes and was referred for a glaucoma evaluation. On initial evaluation, her IOP was 25 mm Hg in the right eye and 26 mm Hg in the left eye. Central corneal thickness measured 592 µm in the right eye and 581 µm in the left eye. Her angles were open to gonioscopy without any peripheral anterior synechia. She had 1+ nuclear sclerosis with a corrected distance visual acuity (CDVA) of 20/25 in the right eye and 20/30- in the left eye and uncorrected near visual acuity of J1+ in each eye. Her nerves were 0.85 mm in the right eye and 0.75 mm in the left eye. Optical coherence tomography (OCT) showed retinal nerve fiber layer thinning and a dense superior arcuate scotoma into fixation in her right eye, and superior and inferior arcuate scotomas in her left eye (Figures 1 and 2JOURNAL/jcrs/04.03/02158034-202307000-00019/figure1/v/2023-06-26T195222Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202307000-00019/figure2/v/2023-06-26T195222Z/r/image-tiff, Supplemental Figures 1 and 2, available at http://links.lww.com/JRS/A882 and http://links.lww.com/JRS/A883). She was successively trialed on fixed combination brimonidine-timolol, dorzolamide, and netarsudil, in addition to her latanoprost, but her IOP remained in the mid- to upper 20s in both eyes. The addition of acetazolamide lowered the pressure to 19 mm Hg in both eyes, but she tolerated it poorly. Methazolamide was also attempted with similar side effects. We elected to perform left eye cataract surgery combined with 360-degree viscocanaloplasty and insertion of a Hydrus microstent (Alcon Laboratories, Inc.). Surgery was uncomplicated with IOP of 16 mm Hg on postoperative day 1 with no glaucoma medications. However, by postoperative week 3, IOP returned to 27 mm Hg, and despite restarting latanoprost-netarsudil and finishing her steroid taper, IOP remained at 27 mm Hg by postoperative week 6. Brimonidine-timolol was added back to her left eye regimen and at postoperative week 8, IOP had elevated to 45 mm Hg. Maximizing her therapy with the addition of topical dorzolamide and oral methazolamide brought her IOP back down to 30 mm Hg. At that point, the decision was made to proceed with trabeculectomy of the left eye. The trabeculectomy was uneventful. However, postoperative attempts to augment filtration were rendered less successful by extremely thick Tenon layer. At her most recent follow-up the pressure in the left eye was mid-teens with brimonidine-timolol and dorzolamide. Her right eye IOP is in the upper 20s on maximum topical therapy. Knowing her postoperative course in the left eye, how would you manage the right eye? In addition to currently available options, would you consider a supraciliary shunt such as the MINIject (iSTAR) if such a device were U.S. Food and Drug Administration (FDA)-approved?

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.

Descemetorhexis Without Endothelial Keratoplasty Versus DMEK for Treatment of Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To compare the visual outcomes and associated morbidity of patients with Fuchs endothelial corneal dystrophy who were treated with either Descemet membrane endothelial keratoplasty (DMEK) or descemetorhexis without endothelial keratoplasty (DWEK). METHODS: This is a retrospective comparative cohort study of 27 eyes with mild to moderate Fuchs dystrophy (with corneal guttae/edema limited to the central cornea with relatively clear periphery) that were treated at the University of Pittsburgh Medical Center from 2015 to 2017 with either DMEK (n = 15) or DWEK (n = 12). Descemetorhexis was performed by removing the central 4 mm of diseased Descemet membrane at the end of phacoemulsification for cataract surgery. Visual acuity was measured using the Snellen chart and then converted to logMAR for analysis. RESULTS: Average postoperative pinhole visual acuity was 20/25 - 1 (logMAR 0.16 ± 0.09) for DMEK eyes and 20/30 + 1 (logMAR 0.13 ± 0.10) for DWEK eyes (P = 0.44). The average time to 20/40 vision for DMEK was 2.2 ± 2.8 weeks compared with 7.1 ± 2.7 weeks for DWEK (P < 0.01). In our DMEK group, 8 (53%) patients had adverse events, including increased intraocular pressure (n = 7), anterior chamber inflammation (n = 1), and graft nonadherence (n = 1), with 1 patient requiring anterior chamber paracentesis (6.7%) and 1 patient (6.7%) requiring a rebubbling procedure. Our DWEK group had no adverse events (P < 0.01). CONCLUSIONS: DWEK effectively treats select patients with mild to moderate Fuchs dystrophy with equivalent visual outcomes compared with the current standard of care, DMEK. Although the recovery time may be longer, DWEK patients had reduced adverse events and need for additional procedures and did not require long-term immunosuppression or donor corneal tissue.

Histology-Stratified Tumor Control and Patient Survival After Stereotactic Radiosurgery for Pineal Region Tumors: A Report From the International Gamma Knife Research Foundation.

BACKGROUND: Pineal region tumors represent a rare and histologically diverse group of lesions. Few studies are available to guide management and the outcomes after stereotactic radiosurgery (SRS). METHODS: Patients who underwent SRS for a pineal region tumor and for whom at least 6 months of imaging follow-up was available were retrospectively assessed in 5 centers. Data were collected from the medical record and histology level analyses were performed, including actuarial tumor control and survival analyses. RESULTS: A total of 70 patients were treated between 1989 and 2014 with a median follow-up of 47 months. Diagnoses were pineocytoma (37%), pineoblastoma (19%), pineal parenchymal tumor of intermediate differentiation (10%), papillary tumor of the pineal region (9%), germinoma (7%), teratoma (3%), embryonal carcinoma (1%), and unknown (14%). Median prescription dose was 15 Gy at the 50% isodose line. Actuarial local control and survival rates were 81% and 76% at 20 years for pineocytoma, 50% and 56% at 5 years for pineal parenchymal tumor of intermediate differentiation, 27% and 48% at 5 years for pineoblastoma, 33% and 100% at 5 years for papillary tumor of the pineal region, 80% and 80% at 20 years for germinoma, and 61% and 67% at 5 years for tumors of unknown histology. New focal neurological deficit, Parinaud syndrome, and hydrocephalus occurred in 9%, 7%, and 3% of cases, respectively. CONCLUSIONS: SRS is a safe modality for the management of pineal region tumors. Its specific role is highly dependent on tumor histology. As such, all efforts should be made to obtain a reliable histologic diagnosis.

Stereotactic radiosurgery for recurrent vestibular schwannoma after previous resection.

OBJECTIVE The goal of this retrospective cohort study was to assess long-term outcomes in patients with vestibular schwannoma (VS) who underwent stereotactic radiosurgery (SRS) after initial microsurgical resection. METHODS From the authors' database of 1770 patients with VS, the authors retrospectively analyzed data from 173 Gamma Knife SRS procedures for VS after 1 (128 procedures) or multiple (45 procedures) microsurgical resections. The median length of the interval between the last resection and SRS was 42 months (range 2-329 months). The median length of clinical follow-up was 74 months (range 6-285 months). Progression-free survival after SRS was determined with Kaplan-Meier analysis. RESULTS At the time of SRS, the hearing of 161 patients (93%) was Gardner-Robertson Class V, and 81 patients (47%) had facial neuropathy (i.e., facial function with House-Brackmann [HB] grades of III-VI), 87 (50%) had trigeminal neuropathy, and 71 (41%) reported imbalance or disequilibrium disorders. The median tumor volume was 2.7 cm3 (range 0.2-21.6 cm3), and the median dose to the tumor margin was 13 Gy (range 11-20 Gy). Radiosurgery controlled growth of 163 (94%) tumors. Progression-free survival after SRS was 97% at 3 years, 95% at 5 years, and 90% at 10 years. Four patients with delayed tumor progression underwent repeat SRS at a median of 35 months (range 23-64 months) after the first SRS. Four patients (2.3%) with tumor progression underwent repeat resection at a median of 25 months (range 19-33 months). Among the patients with any facial dysfunction (indicated by HB grades of II-VI), 19% had improvement in this condition after SRS, and 5.5% with some facial function (indicated by HB grades of I-V) developed more facial weakness. Among patients with trigeminal neuropathy, 20% had improvement in this condition, and 5.8% developed or had worsened trigeminal neuropathy after SRS. CONCLUSIONS Stereotactic radiosurgery offered a safe and effective long-term management strategy for VS patients whose tumors remained or recurred after initial microsurgery.

Hearing subclassification may predict long-term auditory outcomes after radiosurgery for vestibular schwannoma patients with good hearing.

OBJECTIVE In the era of MRI, vestibular schwannomas are often recognized when patients still have excellent hearing. Besides success in tumor control rate, hearing preservation is a main goal in any procedure for management of this population. The authors evaluated whether modified auditory subclassification prior to radiosurgery could predict long-term hearing outcome in this population. METHODS The authors reviewed a quality assessment registry that included the records of 1134 vestibular schwannoma patients who had undergone stereotactic radiosurgery during a 15-year period (1997-2011). The authors identified 166 patients who had Gardner-Robertson Class I hearing prior to stereotactic radiosurgery. Fifty-three patients were classified as having Class I-A (no subjective hearing loss) and 113 patients as Class I-B (subjective hearing loss). Class I-B patients were further stratified into Class I-B1 (pure tone average ≤ 10 dB in comparison with the contralateral ear; 56 patients), and I-B2 (> 10 dB compared with the normal ear; 57 patients). At a median follow-up of 65 months, the authors evaluated patients' hearing outcomes and tumor control. RESULTS The median pure tone average elevations after stereotactic radiosurgery were 5 dB, 13.5 dB, and 28 dB in Classes I-A, I-B1, and I-B2, respectively. The median declines in speech discrimination scores after stereotactic radiosurgery were 0% for Class I-A (p = 0.33), 8% for Class I-B1 (p < 0.0001), and 40% for Class I-B2 (p < 0.0001). Serviceable hearing preservation rates were 98%, 73%, and 33% for Classes I-A, I-B1, and I-B2, respectively. Gardner-Robertson Class I hearing was preserved in 87%, 43%, and 5% of patients in Classes I-A, I-B1, and I-B2, respectively. CONCLUSIONS Long-term hearing preservation was significantly better if radiosurgery was performed prior to subjective hearing loss. In patients with subjective hearing loss, the difference in pure tone average between the affected ear and the unaffected ear was an important factor in long-term hearing preservation.

Early radiosurgery provides superior pain relief for trigeminal neuralgia patients.

OBJECTIVE: We evaluated factors associated with better outcomes after stereotactic radiosurgery (SRS) when it was performed as the first surgical procedure for medically refractory trigeminal neuralgia. METHODS: A total of 121 patients (median age 72 years) with medically refractory pain and no prior surgery underwent Gamma Knife SRS as their initial surgical procedure for trigeminal neuralgia. Using a single 4-mm isocenter, patients received an average maximum dose of 80 Gy, delivered to the trigeminal nerve target defined by intraoperative MRI. The median follow-up was 36 months. RESULTS: Pain relief (Barrow Neurological Institute [BNI] score I-IIIa) was achieved in 107 (88%) patients at a median time of 1 month. Patients who underwent earlier SRS (within 3 years of pain onset) had a shorter interval until pain relief (1 week, p < 0.001), had a longer interval of pain relief off medication (BNI-I, p < 0.001), and had a longer duration of adequate pain control (BNI-I-IIIa, p < 0.001). Median pain-free intervals for patients who underwent SRS at 1, 2, 3, and more than 3 years after trigeminal neuralgia diagnosis were 68, 37, 36, and 10 months, respectively. Patients who responded to SRS within the first 3 weeks after SRS had a longer duration of complete pain relief compared to those with longer response times (p = 0.001). Fifteen patients (12%) reported new sensory dysfunction after SRS. CONCLUSION: Early SRS as the initial surgical procedure for management of refractory trigeminal neuralgia was associated with faster, better, and longer pain relief when compared to late SRS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with medically refractory trigeminal neuralgia, early stereotactic radiosurgery as the initial procedure provides faster, better, and longer pain relief.

The frontotemporal lobar degeneration risk factor, TMEM106B, regulates lysosomal morphology and function.

Haploinsufficiency of Progranulin (PGRN), a gene encoding a secreted glycoprotein, is a major cause of frontotemporal lobar degeneration with ubiquitin (FTLD-U) positive inclusions. Single nucleotide polymorphisms in the TMEM106B gene were recently discovered as a risk factor for FTLD-U, especially in patients with PGRN mutations. TMEM106B is also associated with cognitive impairment in amyotrophic lateral sclerosis patients. Despite these studies, little is known about TMEM106B at molecular and cellular levels and how TMEM106B contributes to FTLD. Here, we show that TMEM106B is localized in the late endosome/lysosome compartments and TMEM106B levels are regulated by lysosomal activities. Ectopic expression of TMEM106B induces morphologic changes of lysosome compartments and delays the degradation of endocytic cargoes by the endolysosomal pathway. Furthermore, overexpression of TMEM106B correlates with elevated levels of PGRN, possibly by attenuating lysosomal degradation of PGRN. These results shed light on the cellular functions of TMEM106B and the roles of TMEM106B in the pathogenesis of FTLD-U with PGRN mutations.