Targeting the chromatin binding of exportin-1 disrupts NFAT and T cell activation.

Exportin-1 (XPO1/CRM1) plays a central role in the nuclear-to-cytoplasmic transport of hundreds of proteins and contributes to other cellular processes, such as centrosome duplication. Small molecules targeting XPO1 induce cytotoxicity, and selinexor was approved by the Food and Drug Administration in 2019 as a cancer chemotherapy for relapsed multiple myeloma. Here, we describe a cell-type-dependent chromatin-binding function for XPO1 that is essential for the chromatin occupancy of NFAT transcription factors and thus the appropriate activation of T cells. Additionally, we establish a class of XPO1-targeting small molecules capable of disrupting the chromatin binding of XPO1 without perturbing nuclear export or inducing cytotoxicity. This work defines a broad transcription regulatory role for XPO1 that is essential for T cell activation as well as a new class of XPO1 modulators to enable therapeutic targeting of XPO1 beyond oncology including in T cell-driven autoimmune disorders.

Modeling the effects of glaucoma surgery on intraocular pressure.

Minimally invasive glaucoma surgeries (MIGS) offer an effective way to lower intraocular pressure without inducing extensive trauma to the anterior segment. In order to predict their efficacy, an analytical model of the conventional aqueous humor outflow pathway is developed using a resistor network. The model describes outflow through the normal eye and allows for the effects of geometric changes in the outflow pathway as IOP changes. By selectively removing these resistors, the model can be used to examine and predict the outcomes of several surgical procedures currently used to treat glaucoma. Treatments examined include traditional trabeculectomy, several ab interno methods for trabeculotomy and trabeculectomy, as well as recently developed trabecular stents that bypass the trabecular meshwork and dilate Schlemm canal. The model's predictions for the efficacy of these procedures generally matched well with the efficacy determined in experimental studies, although it tended to somewhat overestimate the efficacy of these procedures. Matching the model to experimental data indicated that a partial trabeculotomy substantially increases flow to collector channels within that region and approximately 1.5 clock hours past the ends of the trabeculotomized region. Similarly, trabecular bypass stents substantially increase flow to collector channels up to 1.5 clock hours past the open ends of the stent. The resistor model we have developed can be used to predict the efficacy of a variety of MIGS procedures. Circumferential flow in Schlemm canal extends the efficacy of MIGS, but this effect is limited to a few clock hours.

Emergency Computed Tomography: How Misinterpretations Vary According to the Periods of the Nightshift?

OBJECTIVE: To evaluate the accuracy of initial computed tomography (CT) interpretations made by radiology residents during nightshifts in the emergency department. METHODS: Preliminary CT reports performed by radiology residents during 120 consecutive nightshifts (08:30 pm to 08:30 am) were reviewed, attendings' final interpretation being the reference standard. Nightshifts were divided into four consecutive periods of 3 hours. Major misinterpretations were related to potentially life-threatening conditions if not treated immediately after CT. The rate of misinterpretations was calculated for all CT examinations, separately for nightshift's periods and for residents' training years. RESULTS: Misinterpretations were recorded in 155 (7.4%) of 2102 CT examinations, 0.6% (13/2102) were major. There were 2.2% (4/186) major misinterpretations that occurred during the last period of the nightshift versus 0.4% (9/1916) during the first periods of the night (P < 0.05). Of all misinterpretations, 8.5% (130/1526) were made by third- and fourth-year residents and 4.3% (25/576) by fifth-year residents (P < 0.005). CONCLUSIONS: Major misinterpretations occur at the end of the nightshift, which may be explained by the fatigue effect. The rate of misinterpretations is lower among fifth-year residents, which may be related to their prior experience in reading emergency cases.

[Lactate and acute mesenteric ischemia: diagnostic value]. / Lactate et ischémie mésentérique aiguë†: utilité diagnostique.

Acute mesenteric ischemia is a rare diagnosis with a very high mortality rate. It is often suspected in case of severe abdominal pain, disproportional to the findings of physical examination. The definite diagnosis is confirmed by CT-angiography and surgical exploration, but the measurement of blood L-lactate often takes place during the diagnostic work-up when this pathology is suspected. This review shows that there is no biological marker with sufficient sensitivity and specificity to confirm or rule out acute mesenteric ischemia. L-lactate measurement is easy to perform, but its diagnostic performance is insufficient to avoid a CT-angiography, whatever the pre-test clinical probability of acute mesenteric ischemia. These conclusions are supported by the current recommendations of the World Society of Emergency Surgery.

L'ischémie mésentérique aiguë est un diagnostic rare au taux de mortalité très élevé. Elle est souvent suspectée en cas de douleurs abdominales sévères et disproportionnelles aux résultats de l'examen physique. Le diagnostic définitif s'obtient par angio-CT et exploration chirurgicale, mais le dosage du L-lactate intervient fréquemment lors de la stratégie diagnostique au moment de la suspicion clinique. Cet article met en évidence qu'il n'existe pas de marqueur biologique unique suffisamment sensible et spécifique pour confirmer ou exclure une ischémie mésentérique aiguë. Le dosage du L-lactate est rapide, mais sa performance diagnostique ne permet pas de surseoir à l'angio-CT, et ce quelle que soit la probabilité clinique prétest d'ischémie mésentérique. Ces conclusions sont soutenues par les recommandations des sociétés de chirurgie.

Five-Year Outcomes of Graft-Free Tube Shunts and Risk Factors for Tube Exposures in Glaucoma.

PRCIS: Use of a scleral tunnel technique instead of a patch graft can be considered in most cases of tube shunt implantation. Grafts may still be considered in younger (<65 y old) East Asians. PURPOSE: (1) To assess the risk factors for tube exposure with a graft-free implantation technique and (2) to examine 5-year outcomes of graft-free tube shunt insertion. METHODS: This was a retrospective case series of 204 consecutive eyes undergoing a glaucoma tube shunt implantation with a scleral tunnel technique in lieu of a graft. Preoperative and postoperative best-corrected visual acuity, intraocular pressure, and number of glaucoma medications were compared. Failure was defined as the following: (1) intraocular pressure >21 mm Hg or ≤5 mm Hg on 2 consecutive visits after 3 mo; (2) required additional glaucoma surgery; (3) loss of light perception. Univariable and multivariable regression analyses were conducted to identify risk factors of tube exposures. RESULTS: Intraocular pressure and the number of glaucoma medications were significantly decreased at all postoperative time points ( P <0.001). Success rates were 91% at year 1, 75% at year 3, and 67% at year 5. The most common early (<3 mo) complication was tube malpositioning. The most common late (>3 mo to 5 y) complications were corneal complications and uncontrolled intraocular pressure. By year 5, 6.9% of tubes were exposed. Multivariable regression showed that age less than 65 years old (odds ratio: 3.66, P =0.04) and East Asian ethnicity (odds ratio: 3.36, P =0.04) were associated with significantly increased risk of tube exposure. CONCLUSIONS: Graft-free glaucoma tube implantation has comparable long-term outcomes and complication rates to shunts with a graft. Younger (<65 y old) East Asians are at greater risk of tube exposure without a graft.

Lipid-Restricted Culture Media Reveal Unexpected Cancer Cell Sensitivities.

Cancer cell culture models frequently rely on fetal bovine serum as a source of protein and lipid factors that support cell survival and proliferation; however, serum-containing media imperfectly mimic the in vivo cancer environment. Recent studies suggest that typical serum-containing cell culture conditions can mask cancer dependencies, for example, on cholesterol biosynthesis enzymes, that exist in vivo and emerge when cells are cultured in media that provide more realistic levels of lipids. Here, we describe a high-throughput screen that identified fenretinide and ivermectin as small molecules whose cytotoxicity is greatly enhanced in lipid-restricted media formulations. The mechanism of action studies indicates that ivermectin-induced cell death involves oxidative stress, while fenretinide likely targets delta 4-desaturase, sphingolipid 1, a lipid desaturase necessary for ceramide synthesis, to induce cell death. Notably, both fenretinide and ivermectin have previously demonstrated in vivo anticancer efficacy despite their low cytotoxicity under typical cell culture conditions. These studies suggest ceramide synthesis as a targetable vulnerability of cancer cells cultured under lipid-restricted conditions and reveal a general screening strategy for identifying additional cancer dependencies masked by the superabundance of medium lipids.

Electrophile Determines Cellular Phenotypes among XPO1-Targeting Small Molecules.

Covalent drug discovery has experienced a renaissance, with numerous electrophilic small molecules recently gaining FDA approval. Many structurally diverse electrophilic small molecules target exportin-1 (XPO1/CRM1) at cysteine 528, including the selective inhibitor of nuclear export (SINE) selinexor, which was FDA-approved as an anticancer agent in 2019. Emerging evidence supports additional pharmacological classes of XPO1 modulators targeting Cys528, including the selective inhibitors of transcriptional activation (SITAs) and probes that induce rapid degradation of XPO1. Here, we analyzed structure-activity relationships across multiple structural series of XPO1 Cys528-targeting probes. We observe that the electrophilic moiety of Cys528-targeting small molecules plays a decisive role in the cellular behavior observed, with subtle changes in electrophile structure being sufficient to convert XPO1-targeting probes to different pharmacological classes. This investigation represents a unique case study in which the electrophile functionality used to target a specific cysteine determines the pharmacological effect among diverse XPO1-targeting small molecules.

Beware the Black-Box of Medical Image Generation: an Uncertainty Analysis by the Learned Feature Space.

Deep neural networks (DNNs) are the primary driving force for the current development of medical imaging analysis tools and often provide exciting performance on various tasks. However, such results are usually reported on the overall performance of DNNs, such as the Peak signal-to-noise ratio (PSNR) or mean square error (MSE) for imaging generation tasks. As a black-box, DNNs usually produce a relatively stable performance on the same task across multiple training trials, while the learned feature spaces could be significantly different. We believe additional insightful analysis, such as uncertainty analysis of the learned feature space, is equally important, if not more. Through this work, we evaluate the learned feature space of multiple U-Net architectures for image generation tasks using computational analysis and clustering analysis methods. We demonstrate that the learned feature spaces are easily separable between different training trials of the same architecture with the same hyperparameter setting, indicating the models using different criteria for the same tasks. This phenomenon naturally raises the question of which criteria are correct to use. Thus, our work suggests that assessments other than overall performance are needed before applying a DNN model to real-world practice.

Inhibition of SC4MOL and HSD17B7 shifts cellular sterol composition and promotes oligodendrocyte formation.

While the cholesterol biosynthesis pathway has been extensively studied, recent work has forged new links between inhibition of specific sterol pathway enzymes, accumulation of their unique sterol substrates, and biological areas as diverse as cancer, immunology, and neurodegenerative disease. We recently reported that dozens of small molecules enhance formation of oligodendrocytes, a glial cell type lost in multiple sclerosis, by inhibiting CYP51, Sterol 14-reductase, or EBP and inducing cellular accumulation of their 8,9-unsaturated sterol substrates. Several adjacent pathway enzymes also have 8,9-unsaturated sterol substrates but have not yet been evaluated as potential targets for oligodendrocyte formation or in many other biological contexts, in part due to a lack of available small-molecule probes. Here, we show that genetic suppression of SC4MOL or HSD17B7 increases the formation of oligodendrocytes. Additionally, we have identified and optimized multiple potent new series of SC4MOL and HSD17B7 inhibitors and shown that these small molecules enhance oligodendrocyte formation. SC4MOL inhibitor CW4142 induced accumulation of SC4MOL's sterol substrates in mouse brain and represents an in vivo probe of SC4MOL activity. Mechanistically, the cellular accumulation of these 8,9-unsaturated sterols represents a central driver of enhanced oligodendrocyte formation, as exogenous addition of purified SC4MOL and HSD17B7 substrates but not their 8,9-saturated analogs promotes OPC differentiation. Our work validates SC4MOL and HSD17B7 as novel targets for promoting oligodendrocyte formation, underlines a broad role for 8,9-unsaturated sterols as enhancers of oligodendrocyte formation, and establishes the first high-quality small molecules targeting SC4MOL and HSD17B7 as novel tools for probing diverse areas of biology.

XEN Gel Stent Open Conjunctiva Technique: A Practical Approach Paper.

The Xen Gel Stent lowers intraocular pressure by shunting aqueous humor to the subconjunctival space. While published studies include both open conjunctiva and closed conjunctiva approaches, most publications feature a closed conjunctiva, ab interno approach. While this approach is widely used, other approaches may be preferred for some patients. This paper provides details on surgical steps and tips for enhancing outcomes for an open conjunctiva technique for the implantation of the Xen Gel Stent, as well as reasoning as to when this approach should be used.

Pickering Bubbles as Dual-Modality Ultrasound and Photoacoustic Contrast Agents.

Microbubbles (MBs) stabilized by particle surfactants (i.e., Pickering bubbles) have better thermodynamic stability compared to MBs stabilized by small molecules as a result of steric hindrance against coalescence, higher diffusion resistance, and higher particle desorption energy. In addition, the use of particles to stabilize MBs that are typically used as an ultrasound (US) contrast agent can also introduce photoacoustic (PA) properties, thus enabling a highly effective dual-modality US and PA contrast agent. Here, we report the use of partially reduced and functionalized graphene oxide as the sole surfactant to stabilize perfluorocarbon gas bubbles in the preparation of a dual-modality US and PA agent, with high contrast in both imaging modes and without the need for small-molecule or polymer additives. This approach offers an increase in loading of the PA agent without destabilization and increased thickness of the MB shell compared to traditional systems, in which the focus is on adding a PA agent to existing MB formulations.

Synergistic Combination of Oncolytic Virotherapy and Immunotherapy for Glioma.

PURPOSE: We hypothesized that the combination of a local stimulus for activating tumor-specific T cells and an anti-immunosuppressant would improve treatment of gliomas. Virally encoded IL15Rα-IL15 as the T-cell activating stimulus and a prostaglandin synthesis inhibitor as the anti-immunosuppressant were combined with adoptive transfer of tumor-specific T cells. EXPERIMENTAL DESIGN: Two oncolytic poxviruses, vvDD vaccinia virus and myxoma virus, were each engineered to express the fusion protein IL15Rα-IL15 and a fluorescent protein. Viral gene expression (YFP or tdTomato Red) was confirmed in the murine glioma GL261 in vitro and in vivo. GL261 tumors in immunocompetent C57BL/6J mice were treated with vvDD-IL15Rα-YFP vaccinia virus or vMyx-IL15Rα-tdTr combined with other treatments, including vaccination with GARC-1 peptide (a neoantigen for GL261), rapamycin, celecoxib, and adoptive T-cell therapy. RESULTS: vvDD-IL15Rα-YFP and vMyx-IL15Rα-tdTr each infected and killed GL261 cells in vitro. In vivo, NK cells and CD8+ T cells were increased in the tumor due to the expression of IL15Rα-IL15. Each component of a combination treatment contributed to prolonging survival: an oncolytic virus, the IL15Rα-IL15 expressed by the virus, a source of T cells (whether by prevaccination or adoptive transfer), and prostaglandin inhibition all synergized to produce elimination of gliomas in a majority of mice. vvDD-IL15Rα-YFP occasionally caused ventriculitis-meningitis, but vMyx-IL15Rα-tdTr was safe and effective, causing a strong infiltration of tumor-specific T cells and eliminating gliomas in 83% of treated mice. CONCLUSIONS: IL15Rα-IL15-armed oncolytic poxviruses provide potent antitumor effects against brain tumors when combined with adoptive T-cell therapy, rapamycin, and celecoxib.

The role of extracellular vesicles and PD-L1 in glioblastoma-mediated immunosuppressive monocyte induction.

BACKGROUND: Immunosuppression in glioblastoma (GBM) is an obstacle to effective immunotherapy. GBM-derived immunosuppressive monocytes are central to this. Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule, expressed by GBM cells and GBM extracellular vesicles (EVs). We sought to determine the role of EV-associated PD-L1 in the formation of immunosuppressive monocytes. METHODS: Monocytes collected from healthy donors were conditioned with GBM-derived EVs to induce the formation of immunosuppressive monocytes, which were quantified via flow cytometry. Donor-matched T cells were subsequently co-cultured with EV-conditioned monocytes in order to assess effects on T-cell proliferation. PD-L1 constitutive overexpression or short hairpin RNA-mediated knockdown was used to determined the role of altered PD-L1 expression. RESULTS: GBM EVs interact with both T cells and monocytes but do not directly inhibit T-cell activation. However, GBM EVs induce immunosuppressive monocytes, including myeloid-derived suppressor cells (MDSCs) and nonclassical monocytes (NCMs). MDSCs and NCMs inhibit T-cell proliferation in vitro and are found within GBM in situ. EV PD-L1 expression induces NCMs but not MDSCs, and does not affect EV-conditioned monocytes T-cell inhibition. CONCLUSION: These findings indicate that GBM EV-mediated immunosuppression occurs through induction of immunosuppressive monocytes rather than direct T-cell inhibition and that, while PD-L1 expression is important for the induction of specific immunosuppressive monocyte populations, immunosuppressive signaling mechanisms through EVs are complex and not limited to PD-L1.

A Case of Pseudomonas Orbital Cellulitis Following Glaucoma Device Implantation.

PURPOSE: Orbital cellulitis is a rare complication of aqueous tube shunt surgery. Nine cases have been described in the literature, though the microbiologic etiology is rarely reported. Management with intravenous antibiotics and/or explantation has been described. METHODS: This is a case report and literature review. CASE: A 64-year-old woman developed pain, periorbital swelling, limited extraocular motility, proptosis, and conjunctival injection 3 days following implantation of an Ahmed Glaucoma Valve. Computed tomography of the orbits with contrast showed soft tissue fat stranding consistent with orbital inflammation. Initial medical management with topical and intravenous ceftriaxone and vancomycin was unsuccessful. Surgical removal of the implant was performed and intraoperative cultures demonstrated florid Pseudomonas aeruginosa growth. Antibiotic coverage was changed to Piperacillin-Tazobactam for 3 days, with eventual resolution of her orbital symptoms. CONCLUSIONS: We report the first case of orbital cellulitis after implantation of a glaucoma device associated with P. aeruginosa. Failure of intravenous and topical antibiotics led to explantation of the valve and targeted intravenous antibiotic therapy with subsequent clinical improvement.

Intraoperative complication rates in cataract surgery performed by ophthalmology resident trainees compared to staff surgeons in a Canadian academic center.

PURPOSE: To compare the intraoperative complication rates in cataract surgery performed by resident trainees and staff ophthalmologists. SETTING: Kensington Eye Institute, University of Toronto, Toronto, Canada. DESIGN: Prospective case series. METHODS: This study included 8738 consecutive cases of primary phacoemulsification cataract surgery performed by staff surgeons and resident trainees from January to December 2016. There were no exclusion criteria. Data collected included the level of resident training, case complexity, degree of resident involvement, and intraoperative complications. Primary outcome measures included intraoperative complication rates and level of complexity of cataract surgeries performed by resident trainees and staff surgeons. RESULTS: Resident trainees were involved in 44% of surgeries. Of those, 82% were completed in their entirety by a resident and 18% were performed by both the staff surgeon and resident. Staff surgeons performed 56% of all surgeries without resident involvement. Sixty-seven percent of surgeries were simple and 33% were complex, with small pupil or intraoperative floppy-iris syndrome being the most common reason for complex cases. For simple cases, there was no difference in the overall complication rates (1.7% and 2.0%; P = .52), posterior capsule rupture rates (0.9% and 0.8%; P = .76), or vitreous loss rates (0.4% and 0.2%; P = .08) between staff and residents, respectively. CONCLUSION: There were no differences in complication rates between the two groups.

Congenital Vomer Agenesis: A Rare and Poorly Understood Condition Revealed by Cone Beam CT.

Isolated congenital vomer agenesis is a very rare and poorly understood condition. In the context of dental work-up by cone-beam computed tomography (CBCT), the explored volume of the facial bones occasionally reveals incidental abnormalities. We report the case of a 13-year old Caucasian female who underwent CBCT for the pre-treatment evaluation of primary failure of tooth eruption affecting the permanent right upper and inferior molars. CBCT depicted a large defect of the postero-inferior part of the nasal septum without associated soft tissue abnormality and without cranio-facial malformation or cleft palate. In the absence of a history of trauma, chronic inflammatory sinonasal disease, neoplasia and drug abuse, a posterior nasal septum defect warrants the diagnosis of vomer agenesis. A discussion of this condition and of salient CBCT features is provided.

Reliability of the Maximal Step Length Test and Its Correlation with Motor Function in Chronic Stroke Survivors.

OBJECTIVE: This study aimed to (1) investigate the interrater, intrarater, and test-retest reliabilities, as well as the minimal detectable change, of the Maximal Step Length test (MSL) in stroke survivors, (2) examine the concurrent validity of MSL with other stroke-specific impairment measurements in stroke survivors, and (3) compare the MSL performances of stroke survivors and those of age-matched healthy older adults in different directions. DESIGN: Cross-sessional study. SETTING: University-based research laboratory. PARTICIPANTS: Stroke survivors (n = 48) and age-matched healthy older adults (n = 39). METHODS: Stroke survivors were assessed with MSL, lower limb muscle strength, Limits of Stability (LOS) Test, Berg Balance Scale (BBS), 5-meter walk test, and Activities-specific Balance Confidence (ABC) scale by two trained assessors in 1 session. Their performance on MSL was reassessed 1 week later to establish the test-retest reliability. Healthy older adults were assessed with MSL only. Intraclass correlation coefficient (ICC) was used to assess the reliability of MSL and Spearman's rho was used to quantify the strength of correlations between MSL and secondary outcomes. Between-group differences of MSL were assessed with the independent t-test. RESULTS: The MSL exhibited excellent intrarater, interrater, and test-retest reliabilities [ICC: 0.885-1.000]. Significant correlations (ρ: 0.447-0.723) were demonstrated between MSLs in most directions and muscle strengths of the affected legs, BBS scores, and walking speeds. The step lengths differed significantly between stroke survivors and healthy older adults in the forward, backward, and sideways directions on both the affected and less affected sides. CONCLUSIONS: The MSL is a reliable, valid, and easily administered test of the stepping capabilities of stroke survivors. Stroke survivors had significant shorter MSLs in all directions than the age-matched healthy older adults.

Determinants for asthma control, quality of life and use of complementary and alternative medicine in asthmatic pediatric patients in four cities.

BACKGROUND: Asthma is a significant chronic health problem worldwide. Management aims at disease control by reducing functional impairment and exacerbations and improving quality of life (QoL). We report a multi-center study to survey asthma control and QoL in four cities in the Pearl River Delta. METHODS: The conjoint survey involved ten Hong Kong pediatric hospitals/units, two Shenzhen hospitals, two Macau hospitals, and two Guangzhou hospitals on asthma control (using Asthma Control Test) and QoL (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ). Acceptability of a treatment is graded as very good/good/fair/poor. RESULTS: Good asthma control was only reported in 80% subjects in Hong Kong, but higher in sister cities (85-94%, P < 0.001). Allergic rhinitis, "incense burning", and "smoker in family" were prevalent among the four cities. Logistic regression showed better control of asthma was associated with better PADQLQ (B = - 0.029, P < 0.001), better acceptability of bronchodilator (B = - 1.488, P = 0.025), negatively with "smoker in family" (B = - 0.83, P = 0.015) and various PADQLQ domains. Conversely, worse PADQLQ was associated with allergic rhinitis severity (B = 4.77, P < 0.001), poor control of asthma (B = 7.56, P < 0.001), increased frequency of traditional Chinese medicine use (B = 1.7, P < 0.05), increased frequency of bronchodilator usage (B = 1.05, P < 0.05), "smoker in family" (B = 4.05, P < 0.05), and incense burning at home (B = 3.9, P < 0.05). CONCLUSIONS: There are some clinical and cultural differences among the four southern Chinese cities within the Guangdong province. This study identifies potentially modifiable environmental and treatment factors associated with poor asthma control and QoL for health-care interventions. Having a smoker in the family is independently associated with poor asthma control and QoL.

Relationship between central corneal thickness and hypotony maculopathy after trabeculectomy.

PURPOSE: To study the relationship of central corneal thickness and other factors and the development of hypotony maculopathy (HM). DESIGN: Prospective case-control study. PARTICIPANTS: Thirteen patients with HM and 25 controls with hypotony (defined as intraocular pressure [IOP] of 6 mmHg or less) without signs of maculopathy after trabeculectomy or combined phacotrabeculectomy. METHODS: Information from consecutive patients and controls was collected in a prospective manner. Factors associated with presence of HM were investigated by comparing the findings in the 2 groups in univariate and multivariate analysis. MAIN OUTCOME MEASURES: The following factors were investigated: demographic factors (age and gender), presenting IOP, central corneal thickness (CCT), refractive error, type of glaucoma surgery, and presence of choroidal effusion, among others. RESULTS: Among the variables evaluated, a significant difference between the 2 groups was observed in the age of the patients (patients with HM being significantly younger: 59+/-20 years vs. 73+/-9 years; P = 0.015) and in CCT (eyes with HM having significantly thicker cornea: 553+/-51 microm vs. 506+/-34 microm; P = 0.004). Both predictive factors (younger age and thicker CCT) persisted as significant in a multivariate logistic regression analysis. The measured IOP during hypotony was similar between eyes with HM and hypotony alone (4.7+/-3.2 mmHg and 3.9+/-1.6 mmHg, respectively; P = 0.649). No differences in gender, type of surgery, presence of choroidal detachment, lens status, or degree of myopia were observed between the 2 groups. CONCLUSIONS: This study shows that patients with hypotony and thinner central corneas have a lower risk of experiencing maculopathy. This association may result from the influence of CCT on applanation tonometry, although we can not rule out that CCT is related to the development of HM by other mechanisms. This study suggests that CCT should be taken in consideration when setting a target pressure after glaucoma filtering surgery, particularly if the target IOP is low.