The TsiogkaSpaeth grid for detection of neurological visual field defects: a validation study.

BACKGROUND: The TsiogkaSpaeth (TS) grid is a new, low-cost, and easy to access portable test for visual field (VF) screening which could be used by clinicians in everyday clinical practice. Our study aimed to determine the validity of an innovative screening grid test for identifying neurological disease-associated VF defects. METHODS: We enrolled two groups of participants: We assessed the one eye of ten consecutive adult patients with different types of neurological disease associated VF defects and ten eyes of controls in each group. The TS grid test was performed in each group. Sensitivity, specificity, and positive and negative predictive values of the TS grid scotoma area were assessed using the 24-2 VF Humphrey field analyzer (HFA) as the reference standard. RESULTS: Sensitivity and specificity of the TS grid test were 100% and 90.91%, respectively. The area under curve was 0.9545 with 95% CI 0.87-1.00. There was a significant correlation between the number of missed locations on the TS grid test and the visual field index of the HFA 24-2 (r = 0.9436, P < .0001). CONCLUSION: The sensitivity and specificity of the TS grid test were high in detecting VF defects in neurological disease. The TS grid test appears to be a reliable, low-cost, and easily accessed alternative to traditional VF tests in diagnosing typical neurological patterns of visual field defects. It would be useful in screening subjects for neurologically derived ocular morbidity in everyday clinical practice and in remote areas deprived of specialized health care services.

Is primary open-angle glaucoma an ocular manifestation of systemic disease?

Primary open-angle glaucoma is currently characterized by a pattern of progressive retinal ganglion cell loss that stems from a complex underlying pathophysiology that remains poorly elucidated. The roles of blood flow and intraocular pressure (IOP) in glaucoma pathogenesis have been extensively studied. Further, it has been established that lowering IOP can slow the progression of glaucoma. In addition, a number of influential factors have emerged and gained momentum over the years. Increasing evidence implicates the contributions of low cerebrospinal fluid pressure, autoimmunity, neurodegeneration, and impaired autoregulation towards glaucoma pathophysiology. We aggregate and explore these different camps of thought that have garnered attention over the last few decades, and, in doing so, aim to challenge the long-standing view of glaucoma as a primary disease of the eye. A shift in our perspective towards understanding glaucoma as an ocular manifestation of systemic dysregulation may lead ultimately to better clinical management of the disease.

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs.

Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤ 0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples. Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons. Of these novel miRNAs, 1,657 (45%) were identified in 43 datasets that were generated by cross-linking followed by Argonaute immunoprecipitation and sequencing (Ago CLIP-seq) and represented 3 of the 13 tissues, indicating that these miRNAs are active in the RNA interference pathway. Moreover, experimental investigation through stem-loop PCR of a random collection of newly discovered miRNAs in 12 cell lines representing 5 tissues confirmed their presence and tissue dependence. Among the newly identified miRNAs are many novel miRNA clusters, new members of known miRNA clusters, previously unreported products from uncharacterized arms of miRNA precursors, and previously unrecognized paralogues of functionally important miRNA families (e.g., miR-15/107). Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7% of the newly discovered miRNAs to be human-specific whereas the majority (94.4%) are primate lineage-specific. Our findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and/or tissue-specific miRNAs that are uncharacterized.

The relationship between contrast sensitivity and retinal nerve fiber layer thickness in patients with glaucoma.

PURPOSE: To evaluate the correlation between contrast sensitivity (CS) and retinal nerve fiber layer (RNFL) in different areas of vision. METHODS: This report is a sub-analysis of a prospective, observational cohort study investigating changes in performance-based assessment, vision-related quality of life, and clinical measures in patients with moderate to advanced glaucoma. The study included 161 participants with at least a 2-year history of glaucoma who underwent annual testing for 4 years. Contrast sensitivity was measured using the Spaeth/Richman contrast sensitivity (SPARCS) test, while RNFL thickness (RNFLT) was measured using Cirrus optical coherence tomography (OCT). Statistical analyses were performed to determine correlations between CS and RNFLT; the correlations were calculated for each annual visit, totaling four correlation coefficients for each patient over the course of 4 years. RESULTS: The SPARCS score in the left upper area of vision correlated the most strongly with the RNFLT of the inferior quadrant for both eyes at each annual visit, specifically in the seven o'clock sector for the left eye and the six o'clock sector for the right eye (p < 0.05). There were no discernible trends for the correlations between the other areas of CS and RNFL quadrants or clock hours over the 4 years of the study. Linear regression between the SPARCS total score and average RNFLT showed a significant direct correlation at each visit (p < 0.01). CONCLUSIONS: Contrast sensitivity in the left upper area of vision for both eyes correlated most strongly with the thickness of the inferior quadrant of the RNFL. These fibers project to the temporal portion of the right occipital lobe, implying a potential center for contrast perception in this area. The longitudinal nature of the study suggests that CS may be a predictive tool for changes in RNFL in patients with glaucoma. Despite this finding, retinal damage and its relationship to CS was diffuse. In addition, SPARCS was shown to predict RNFLT. Further research is warranted to understand how CS can be used as a tool in the clinical setting.

Reversible structural and functional changes after intraocular pressure reduction in patients with glaucoma.

PURPOSE: The aim of this study was to evaluate structural and functional improvement following intraocular pressure (IOP) reduction in patients with glaucoma using Spectral Domain Optical Coherence Tomography (SD-OCT), Visual Field (VF) testing, and Visual Evoked Potentials (VEP). METHODS: A total of 76 eyes from 61 patients underwent SD-OCT, VF and VEP testing. Sixty-two eyes were put in either an acutely high (group 1, IOP > 32 mmHg) or mildly high (group 2, IOP between 22 and 31 mmHg) IOP group and underwent a pressure-lowering intervention. Fourteen eyes with stable glaucoma were controls (group 3, IOP < 22 mmHg). SD-OCT, VF and VEP testing were subsequently performed on all patients at three follow-up visits. Results from these follow-up periods were analyzed for signs of functional and structural improvement. RESULTS: Both group 1 and group 2 patients demonstrated significant decrease in the average cup to disc ratio (p < 0.05) following the intervention. Post-interventional reduction of cup volume was also significant for group 2 patients (p < 0.05). RNFL thickness changes were insignificant. Qualitative grading of VFs by two observers showed improvement in group 1 patients' VFs (p = 0.021). VEP measurements were mostly insignificant, with the exception of High Contrast Latency (LHC) deteriorating for group 2 patients in the first follow-up visit (p = 0.025). CONCLUSIONS: This study provides evidence for structural disc cupping reversal following IOP lowering interventions. These changes were not related to the amount of pressure lowering. While there was evidence of functional improvement as measured by VF testing, VEP was unable to detect any reversible changes.

EVALUATING CONTRAST SENSITIVITY IN AGE-RELATED MACULAR DEGENERATION USING A NOVEL COMPUTER-BASED TEST, THE SPAETH/RICHMAN CONTRAST SENSITIVITY TEST.

BACKGROUND: Contrast sensitivity (CS) is a valuable measure of visual function in patients with age-related macular degeneration (AMD). The authors aimed to compare a novel computer-based test (the Spaeth/Richman Contrast Sensitivity test) with Pelli-Robson test for evaluating CS in patients with AMD. METHODS: In this prospective cross-sectional study, CS was evaluated in patients with various stages of AMD and healthy controls using Spaeth/Richman Contrast Sensitivity test and Pelli-Robson test. Spaeth/Richman Contrast Sensitivity test determined CS scores for 5 areas of vision for each eye (central, superonasal, superotemporal, inferonasal, and inferotemporal) and the total score. Test scores between the two methods were compared using mixed-effects linear regression. Spearman's rank correlation coefficient was used to determine correlations. Test-retest reliability was determined using the intraclass correlation coefficient. RESULTS: Of 35 participants with AMD (54 eyes) and 34 controls (66 eyes), 51% were female and 93% were of European descent. The mean Spaeth/Richman Contrast Sensitivity test score for the central area and each of the 4 peripheral quadrants was significantly lower for patients with AMD versus controls (P < 0.001 for all). The mean Pelli-Robson score was also significantly lower in patients with AMD versus controls (P < 0.001). The intraclass correlation coefficient for Spaeth/Richman Contrast Sensitivity test total score and Pelli-Robson score was 0.87 and 0.92, respectively. CONCLUSION: Spaeth/Richman Contrast Sensitivity test, a novel Internet-based method of testing CS, had significantly lower scores for patients with AMD compared with controls for central and peripheral vision. This test is a valuable tool for assessing CS in AMD.

A prospective, longitudinal, observational cohort study examining how glaucoma affects quality of life and visually-related function over 4 years: design and methodology.

BACKGROUND: The aim of this study is to summarize the design and methodology of a prospective, longitudinal, observational cohort study to investigate how glaucoma affects patients' quality of life and visually-related function over a 4-year period. METHODS/DESIGN: One hundred sixty-one (161) subjects were enrolled in this ongoing study. Patients between the ages of 21-85 years with a minimum 2-year diagnosis of primary open-angle glaucoma, chronic primary angle-closure glaucoma or pseudoexfoliation glaucoma were included. Each patient visited Wills Eye Hospital for a baseline visit. Follow-up is planned for a minimum of 4 years, with annual visits. Each visit includes (1) Clinical evaluation: a slit lamp examination, fundoscopy, intraocular pressure measurement, visual field examination, spectral domain optical coherence tomography, Pelli-Robson Contrast Sensitivity test and the Spaeth-Richman Contrast Sensitivity test; (2) a performance based measure: the Compressed Assessment of Ability Related to Vision; and (3) Subjective measures of vision-related quality of life (the National Eye Institute Visual Functioning Questionnaire 25 and the Modified Glaucoma Symptom Scale). DISCUSSION: The results of this ongoing, prospective, longitudinal study are expected to shed light on the relationships between clinical measures, performance-based measures and subjective measures of well-being, in order to assess changes in the quality of life and the ability to function of patients with glaucoma over time.

Unilateral Prostaglandin-Associated Periorbitopathy: A Syndrome Involving Upper Eyelid Retraction Distinguishable From the Aging Sunken Eyelid.

PURPOSE: To study the effects of prostaglandin analogue drops on the eyelids and adnexa in unilaterally treated subjects with the intention of qualifying, quantifying, and categorizing the characteristics of prostaglandin-associated periorbitopathy (PAP). METHODS: Patients using prostaglandin analogue drops in only 1 eye for at least 1 year were evaluated by masked examiners. Orbital and eyelid measurements were obtained for each patient, and adnexal photographs were taken. PAP was divided into 3 grades based on the presence and severity of fat atrophy and the existence and depth of superior sulcus deformity. Statistical analysis was performed comparing data between treated and untreated eyes. RESULTS: Thirty-three patients meeting eligibility criteria were enrolled, with equal numbers of subjects using latanoprost, travoprost, and bimatoprost. Treated eyes had a statistically significant increase in lagophthalmos (0.62 mm, p < 0.001), superior sulcus deformity/PAP grade (0.72, p < 0.001), and eyelid redness (1.08, p < 0.001). Treated eyes had significantly greater marginal reflex distance 1 measurements (0.89 mm, p = 0.02), highest with bimatoprost and moderate PAP. Treated eyes had relatively greater enophthalmos than untreated eyes. Very few patients noticed or complained about eyelid changes. CONCLUSION: Prostaglandin analogue drops cause adnexal changes and orbital fat atrophy leading to eyelid redness, superior sulcus deformity, higher eyelid crease, and enophthalmos. In contrast to previous studies showing ptosis in PAP, relative upper eyelid retraction was seen in most of our treated eyes. Our novel PAP grading scale may help objectify and categorize this syndrome. Awareness of these signs is critical, as the eyelids and eyes may be affected even in the absence of patient recognition.

Ocular manifestations of 22q11.2 microduplication.

PURPOSE: To report a new ocular manifestation of the dup22q11 syndrome and explore involved genes that may offer insight to mechanisms of pathogenesis. DESIGN: Case series. PARTICIPANTS: Two male patients with this syndrome diagnosed with dup22q11.2. METHODS: Medical records were reviewed. Duplication was detected in the oligo-single nucleotide polymorphism chromosomal microarray and duplicated genes within the segment where determined by literature and database review. Potential associations between the ophthalmologic manifestations and their physiopathology were investigated. MAIN OUTCOME MEASURES: Microarray results and identification of candidate genes within the duplicated segment. RESULTS: Our patients demonstrate previously unreported findings of dup22q11.2, including Marcus Gunn jaw winking, Duane's retraction syndrome, and other abnormal eye movements consistent with a congenital cranial dysinnervation disorder (CCDD), retinal vascular tortuosity, and primary infantile glaucoma. The duplicated segment in case 1 includes SNAP29, which could be linked with the development of retinal vascular tortuosity, and MAPK1, which seems to play a role in axonal development through the semaphorin pathway, which may serve as a candidate gene for CCDD. In case 2, the CLDN5 gene is within the duplicated segment. CLDN5 could be involved in the pathophysiology of glaucoma. CONCLUSIONS: Our cases expand the ocular phenotype for duplication of 22q11 and serve to identify potential candidate genes for the development of CCDD, retinal vascular tortuosity, and glaucoma.

A Health-Related Quality of Life Measure for Patients Who Undergo Minimally Invasive Glaucoma Surgery.

PURPOSE: To develop a patient-reported outcome measure to assess the impact of glaucoma and treatment, including minimally invasive glaucoma surgery (MIGS). DESIGN: Observational study before and after concomitant cataract and Food and Drug Administration-approved implantable MIGS device surgery. SETTING: Survey administration was on a computer, iPad, or similar device. PATIENT POPULATION: 184 adults completed the baseline survey, 124 a survey 3 months after surgery, and 106 the 1-month test-retest reliability survey. The age range was 37 to 89 (average age = 72). Most were female (57%), non-Hispanic White (81%), and had a college degree (56%). MAIN OUTCOME MEASURES: The Glaucoma Outcomes Survey (GOS) assesses functional limitations (27 items), vision-related symptoms (7 items), psychosocial issues (7 items), and satisfaction with microinvasive glaucoma surgery (1 item). These multiple-item scales were scored on a 0 to 100 range, with a higher score indicating worse health. RESULTS: Internal consistency reliability estimates ranged from 0.75 to 0.93, and 1-month test-retest intraclass correlations ranged from 0.83 to 0.92 for the GOS scales. Product-moment correlations among the scales ranged from 0.56 to 0.60. Improvement in visual acuity in the study eye from baseline to the 3-month follow-up was significantly related to improvements in GOS functional limitations (r = 0.18, P = .0485), vision-related symptoms (r = 0.19, P = .0386), and psychosocial concerns (r = 0.18, P = .0503). Responders to treatment ranged from 17% for vision-related symptoms to 48% for functional limitations. CONCLUSIONS: This study supports using the GOS for ophthalmic procedures such as MIGS. Further evaluation of the GOS in different patient subgroups and clinical settings is needed.

Priorities of ophthalmic research.

The purpose of research is to uncover truths, that is to describe reality validly. But all truths are not equally generalizable, and all research is not equally justifiable. For example, the value of a study that requires an N of 100,000 to reach statistical significance (a presumed truth) is likely to be far less than that of a study requiring only an N of 10. Furthermore, the value of research is related to the relevance of the finding to the 'great issues'. In the field of health, the two great issues are function and feeling - the capacity to act and the quality of life. Investigators, universities, mentors, and funding sources need to consider truthfully whether a proposed research project is directed towards uncovering a relevant truth, one that has a reasonable chance of improving function and/or feeling, or leading to findings that will improve function or feeling. The development of a useless or harmful product, the publication of an irrelevant paper, the support of a 'brilliant investigator', and the development of a prestigious department are not adequate justifications for performing research. The consequences of the present system - driven by financial gain, power, and prestige - are exemplified in the comparison of the large amount of funds being expended to improve cataract surgery (which is already an incredibly successful procedure), yet at the same time almost no funds are being spent to study how to detect people with glaucoma who will go blind, fully 1% of the world's population.

Correlation between Central Visual Field Defects and Stereopsis in Patients with Early-to-Moderate Visual Field Loss.

PURPOSE: To investigate the association between stereoacuity and the presence of central visual field defects (CVFDs) due to glaucoma. DESIGN: A prospective, cross-sectional cohort study. PARTICIPANTS: Participants with early-to-moderate glaucoma with a visual acuity better than 20/40, less than a 2-line difference in visual acuity between eyes, and 2 reliable Humphrey visual fields (VFs) (24-2 SITA standard) with mean deviation (MD) in the worse eye better than - 12 dB. METHODS: Stereoacuity was measured using the Titmus stereo test. Participants with a significant field defect (P < 0.005) in any 1 of the central 4 points in the 24-2 SITA standard total deviation map in either eye were classified as having a CVFD. Vision-related quality of life (VR-QOL) was measured using 25-item National Eye Institute Visual Function Questionnaire scores. Logistic regression was used to determine the associations between the level of stereoacuity and age, sex, race, glaucoma type, presence of CVFDs, visual acuity, contrast sensitivity, and VF MD. MAIN OUTCOME MEASURES: Stereoacuity in the CVFD and non-CVFD groups. RESULTS: Sixty-five participants met the inclusion criteria. The mean age of the participants was 64.3 ± 8.0 years, and 64.6% were women. The median stereoacuity was 60 arc seconds (interquartile range [IQR], 40-120 arc seconds). Forty-two (65%) patients had CVFDs, and 23 (35%) patients did not. The median stereoacuity of the CVFD group was worse than that of the non-CVFD group (60 arc seconds [IQR, 50-140 arc seconds] vs. 40 arc seconds [IQR, 40-80 arc seconds], respectively; P = 0.001). The non-CVFD group had a higher percentage of participants with normal stereopsis than the non-CVFD group (61% vs. 21%, respectively; P = 0.001). A multivariable analysis found that the presence of CVFDs was associated with worse stereopsis levels (odds ratio, 4.49; P = 0.021). The CVFD group had a lower Visual Functioning Questionnaire-25 (VFQ-25) composite score (84.0 vs. 91.4; P = 0.004) and lower VFQ-25 subscale scores for general vision, near activities, and mental health (P < 0.05). CONCLUSIONS: Central visual field defects were associated with increased odds of poor stereoacuity in patients with early-to-moderate glaucomatous VF loss. Specifically, patients without CVFDs are more likely to have normal stereopsis and higher VR-QOL than those with CVFDs. Patients with CVFDs should be counseled regarding how depth perception difficulties may affect daily living. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Absence of altered expression of optineurin in primary open angle glaucoma patients.

PURPOSE: To investigate the expression level of the optineurin gene (OPTN) in the blood of primary open angle glaucoma (POAG) patients to determine if altered expression is playing a role in primary open angle glaucoma systemically. METHODS: Patients (n=47) were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. Control subjects (n=27) were recruited who were free from glaucoma by examination. DNA from patient was sequenced to look for possible mutations in the coding region of OPTN or its promoter. RNA was extracted from leukocytes of patients and controls and converted to cDNA by reverse transcriptase enzyme, and quantitative PCR was used to assess expression levels of OPTN and the ß-globulin gene. The ratio of OPTN expression to ß-globulin gene expression for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: No mutation(s) were detected in any of the patients after sequencing the full OPTN gene and its promoter region. Mean OPTN (p≤0.35), and ß-globulin (p≤0.48) gene expression values were statistically similar in POAG patients and controls. OPTN/ß-globulin (p≤0.83) ratios were also indistinguishable between POAG patients and controls. OPTN/ß-globulin ratios were not significantly associated with age, sex, or ethnicity of patients within the POAG group. Similarly, OPTN/ß-globulin ratios were not significantly affected by ethnicity or clinical parameters related to POAG severity including maximum intraocular pressure, vertical cup-to-disk ratio, static perimetry mean deviation, or static perimetry pattern standard deviation. CONCLUSIONS: OPTN expression is not altered in the blood of POAG patients, suggesting that OPTN expression is not changed systemically and implying that other mechanisms are involved in POAG pathogenesis.

Unaltered myocilin expression in the blood of primary open angle glaucoma patients.

PURPOSE: To investigate the expression of the myocilin gene (MYOC) in the blood of primary open angle glaucoma (POAG) patients to determine if altered systemic expression is playing a role. METHODS: Patients (n=47) were eligible for inclusion if they met standard clinical criteria for POAG. Control subjects (n=27) were recruited who were free from glaucoma by examination. RNA was extracted from leukocytes of patients and controls and converted to cDNA by reverse transcriptase enzyme, and quantitative PCR was used to assess expression levels of MYOC and the house keeping gene ß-globulin (HBB). The ratio of MYOC expression to HBB expression for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: Mean gene expression values were statistically similar in POAG patients and controls for both MYOC (p≤0.55) and HBB (p≤0.48). MYOC/HBB ratios were also statistically indistinguishable between POAG patients and controls (p≤0.90). MYOC/HBB ratios were not significantly associated with age, sex, or ethnicity of patients within the POAG group. Similarly, MYOC/HBB ratios were not significantly associated with clinical parameters related to POAG severity, including maximum intraocular pressure, vertical cup-to-disk ratio, static perimetry mean deviation, or static perimetry pattern standard deviation. CONCLUSIONS: MYOC expression is not altered in the blood of POAG patients, unlike MYOC expression in trabecular meshwork (TM) cultures. These results suggests that MYOC expression is not altered systemically but rather that MYOC expression may contribute to POAG pathogenesis in specific tissues such as TM.

Comparison of Central and Peripheral Contrast Sensitivity Between Healthy and Refractive Surgery Patients Using the Spaeth/Richman Contrast Sensitivity (SPARCS) Test.

PURPOSE: To assess contrast sensitivity of central and peripheral vision with a newly developed, internet-based Spaeth/Richman Contrast Sensitivity (SPARCS) test in patients who underwent myopic photorefractive keratectomy (PRK) or femtosecond laser-assisted laser in situ keratomileusis (FSLASIK) refractive surgery in comparison with controls. METHODS: In a retrospective study, a total of 186 eyes from 93 patients were analyzed: 62 eyes from 31 patients for each of the three groups under comparison. Patients who underwent a refractive surgery procedure and controls were evaluated using the SPARCS test. SPARCS scores were obtained for central and four peripheral areas (right upper, right lower, left upper, and left lower quadrants). Total, central, and peripheral SPARCS scores in patients with refractive surgery were compared with controls, adjusting for possible confounders. Multivariate and mixed linear regression models were used. RESULTS: Patients who had PRK had a lower score in all categories compared with the control group: by 5.9 points (95% CI: -9 to -2.8) in the total score, by 1.6 points (95% CI: -3 to -0.3) in the central score, and by 5.5 points (95% CI: -9.4 to -1.6) in the peripheral score. Patients who had FS-LASIK had non-statistically significant lower scores than the control group. CONCLUSIONS: PRK causes a decrease in central and peripheral contrast sensitivity. [J Refract Surg. 2022;38(2):128-133.].

Down-regulation of OPA1 in patients with primary open angle glaucoma.

PURPOSE: Heterozygous optic atrophy type1 (OPA1) mutations are responsible for dominant optic atrophy, and the down regulation of OPA1 expression in patients with Leber hereditary optic neuropathy may imply that Opa1 protein levels in mitochondria play a role in other spontaneous optic neuropathies as well. Mitochondrial and metabolic abnormalities may put the optic nerve at risk in primary open angle glaucoma (POAG), and this preliminary study was designed to investigate whether altered OPA1 expression might be present in the progressive optic neuropathy of POAG. METHODS: Patients were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥ 21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. RNA was extracted from leukocytes and converted to cDNA by reverse transcriptase enzyme, and real time PCR was used to assess expression levels of OPA1 and the ß-globulin (HBB) housekeeping gene. The ratio of OPA1 expression to HBB expression (OPA1/HBB) for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: Forty-three POAG patients and 27 controls were completely phenotyped with a full ophthalmologic examination and static perimetry. Mean age (POAG 67.9 years; controls 61.8 years) and sex (POAG 26 males/17 females; controls 11/16) were similar for the two groups. Mean OPA1/HBB of POAG patients (1.16, SD 0.26) was 18% lower than controls (1.41, SD 0.50), and this difference was statistically significant (p≤0.021). OPA1 expression differed between the groups (p≤0.037), but HBB expression did not differ (p≤0.24). OPA1/HBB was not correlated with any clinical feature of POAG patients. CONCLUSIONS: Transcriptional analysis of peripheral blood leucocytes is a limited model system for studying the consequences of mitochondrial abnormalities in the optic nerve. Nevertheless, OPA1 is known to affect mitochondrial stability and has now been implicated in several spontaneous optic neuropathies. Decreased OPA1 expression in POAG patients is another indication that mitochondrial function, and possibly mitochondrially-induced apoptosis, may play a role in the development of POAG.

A history of the surgical management of glaucoma.

Many new surgeries have been devised since 1856, when von Graefe discovered that iridectomy is an effective surgical method for acute glaucoma treatment. Two years later, De Wecker presented sclerotomy as a procedure for chronic glaucoma. In 1900, internal filtration (cyclodialysis) was developed. In 1932, ciliodestruction was suggested. The four approaches, relief of pupillary block, external filtration, internal filtration, and ciliodestruction, are still the basic techniques of glaucoma surgeries over 100 years later. There have been two basic approaches to lowering eye pressure surgically: increase outflow and decrease inflow of aqueous humor. Although the majority of surgeries used nowadays were introduced in the 1960s, their roots can be traced to the work of surgeons in the 19th century. Trabeculectomy, in use since the mid-1960s, is the most effective glaucoma surgery in terms of intraocular pressure reduction but carries its own limitations. Non-penetrating glaucoma surgeries emerged at the same time trabeculectomy was presented, but they are not used as commonly as trabeculectomy. Molteno introduced the first effective shunt and followed by others. Since 1995, the majority of new surgeries have consisted of new implantable devices including SOLX, iStent, and Ex-PRESS shunt. This article will review the history of glaucoma surgery and describe the fundamentals of different glaucoma procedures.

Improvement in structure and visual function in patients with glaucoma: the possible key to better treatment?

Glaucoma is characterized by retinal ganglion cell loss that can lead to permanent visual loss. Current clinical management practice assumes that glaucomatous visual loss is irreversible; however, there is increasing evidence that permanent vision loss and cell death are preceded by reversible functional and structural changes. We propose that these changes should be considered by glaucoma specialists when treating their patients. We discuss the neurobiological basis of this phenomenon and provide clinical evidence of reversibility in both structure and function. Specifically, we review the findings of visual field testing, contrast sensitivity, electroretinography, and imaging of the optic nerve and their correlation with functional changes. We then discuss the clinical value of these observations in helping guide approaches toward the diagnosis and treatment of patients with glaucoma.

Cataract Surgery (Phacoemulsification with Intraocular Lens Implantation) Combined with Endoscopic Goniosynechialysis for Advanced Primary Angle-Closure Glaucoma.

PURPOSE: To evaluate the efficacy and risk of cataract surgery (phacoemulsification with intraocular lens [IOL] implantation) combined with endoscopic goniosynechialysis (EGSL) for advanced primary angle-closure glaucoma (PACG). DESIGN: Retrospective, continuous case series. PARTICIPANTS: A total of 16 patients (18 eyes) with advanced PACG were enrolled in this study between February 2014 and March 2016. Advanced glaucoma inclusion criteria were based on the method proposed in the Advanced Glaucoma Intervention Study, with a visual field score of 18 points or more. METHODS: All patients underwent cataract surgery with EGSL by the same experienced surgeon. Paired t test and generalized estimating equation analyses were performed. MAIN OUTCOME MEASURES: The extent of peripheral anterior synechiae (PAS), number of intraocular pressure (IOP)-lowering drugs, IOP, best-corrected visual acuity (BCVA), and visual fields before and after surgery. The incidence of complications was recorded. RESULTS: The mean follow-up duration was 13.8 months (standard deviation, 2.7 months). The mean difference (preoperative minus postoperative) in PAS was 202.7° (95% confidence interval [CI], 43.5°). The mean difference (preoperative minus postoperative) in the number of IOP-lowering drugs and IOP was 2.0 (95% CI, ±0.5), and 9.4 mmHg (95% CI, ±2.1 mmHg) respectively. The mean improvement in BCVA was 0.29 logMAR (95% CI, ±0.14). A positive correlation was found between the extent of postoperative PAS and postoperative IOP (B = 8.2; P < 0.001) and also between postoperative PAS and postoperative number of IOP-lowering drugs (B = 28.9; P < 0.001). Anterior chamber hemorrhage and exudation occurred in 4 patients and 2 patients, respectively, after surgery. Posterior capsular opacification occurred in 5 patients after surgery. CONCLUSIONS: Cataract surgery with EGSL could be an effective surgical method for the treatment of advanced PACG.

Vision-Targeted Health-Related Quality-of-Life Survey for Evaluating Minimally Invasive Glaucoma Surgery.

PURPOSE: To develop a vision-targeted health-related quality-of-life instrument for patients with glaucoma who are candidates for minimally invasive glaucoma surgery (MIGS). DESIGN: Development of a health-related quality-of-life instrument. PARTICIPANTS: Twelve practicing ophthalmologists and 41 glaucoma patients. METHODS: A questionnaire was constructed to assess functional limitations, vision-related symptoms, aesthetics, psychosocial issues, and surgical satisfaction for MIGS candidates. Questions were drafted after a review of the literature and subsequently refined based upon input from 1 physician and 4 patient focus groups. Nineteen cognitive interviews were used to ensure that questions were understandable to respondents. RESULTS: The focus group identified the following key issues and concerns as being important to glaucoma patients: functional limitations (eg, driving), bodily discomfort (eg, stinging from drops), changes in appearance (eg, drooping eyelid), and psychosocial concerns (eg, mental burden associated with a diagnosis of glaucoma, financial burden of treatment). Cognitive interviews resulted in the following improvements to the questionnaire: changes in wording to clarify lighting conditions, and additional questions addressing psychosocial issues, such as job loss, severity of disease, and perception of MIGS. CONCLUSIONS: A patient-reported outcomes instrument, the Glaucoma Outcomes Survey, was developed to evaluate MIGS for patients with mild to moderate glaucoma. Next steps include electronic administration to patients selected from the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) registry. An electronic patient-reported outcomes platform will be used to administer the questionnaire before and after MIGS. The questionnaire will improve understanding of how surgical interventions such as MIGS impact vision-targeted health-related quality-of-life in glaucoma patients.