Relative Risks for Dementia among Individuals with Glaucoma: A Meta-Analysis of Observational Cohort Studies

Purpose@#To investigate the relative risks (RRs) for dementia among individuals with glaucoma. @*Methods@#We conducted a search of PubMed, Web of Science, Scopus, and Cochrane databases for observational cohort studies examining the association between glaucoma and dementia until March 2023. Two authors independently screened all titles and abstracts according to predefined inclusion and exclusion criteria. Pooled RR and 95% confidence intervals (CIs) were generated using random-effect models. @*Results@#The meta-analysis included 18 cohort studies conducted in eight countries and involving 4,975,325 individuals. The pooled RR for the association between glaucoma and all-cause dementia was 1.314 (95% CI, 1.099–1.572; I2 = 95%). The pooled RRs for the associations of open-angle glaucoma with Alzheimer dementia and Parkinson disease were 1.287 (95% CI, 1.007–1.646; I2 = 96%) and 1.233 (95% CI, 0.677–2.243; I2 = 73%), respectively. The pooled RRs for the associations of angle-closure glaucoma with all-cause dementia and Alzheimer dementia were 0.978 (95% CI, 0.750–1.277; I2 = 17%) and 0.838 (95% CI, 0.421–1.669; I2 = 16%), respectively. No evidence of publication bias was detected in the Begg-Mazumdar adjusted rank correlation test (p = 0.47). @*Conclusions@#Based on current observational cohort studies, there is evidence supporting that glaucoma is a risk factor for dementia in the adult population.

Clinical Features of the Fellow Eyes of Children with Unilateral Facial Port-Wine Stains and Ipsilateral Glaucoma

Purpose@#To investigate the clinical features of non-affected fellow eyes in patients with unilateral facial port-wine stain (PWS) and ipsilateral secondary glaucoma. @*Methods@#We performed a retrospective analysis of the medical records of 35 patients with unilateral facial PWS glaucoma and those of controls (35 subjects without both facial PWS and glaucoma) between September 1996 and May 2020. We noted patients’ age at the glaucoma diagnosis (for unilateral facial PWS glaucoma patients) or at the initial examination (for controls), cup-to-disc ratio (CDR), and intraocular pressure (IOP). We compared the clinical features between the glaucoma-free eyes in patients with unilateral facial PWS glaucoma and the controls. @*Results@#The mean age at the glaucoma diagnosis for unilateral facial PWS glaucoma patients was 0.56 ± 0.99 years (range, 0.08-4). The mean IOP of the glaucoma-free eyes was 16.68 ± 5.73 mmHg (range, 9-22.9), and the mean CDR was 0.37 ± 0.14 (range, 0.15-0.80) at glaucoma diagnosis. The mean IOP of the glaucoma-free eyes was 14.14 ± 6.29 mmHg (range, 8.1-26.7), and the mean CDR was 0.37 ± 0.12 (range, 0.26-0.82) at final examination. When comparing glaucoma-free eyes of the unilateral facial PWS glaucoma patients with the control group (mean age, 11.2 ± 7.4 years), the mean CDR was significantly greater (0.37 ± 0.12 vs. 0.30 ± 0.08; p = 0.014) but there was no significant difference in the mean IOP (14.14 ± 6.29 mmHg vs. 14.57 ± 2.49 mmHg; p = 0.712). @*Conclusions@#The glaucoma-free eyes of unilateral facial PWS glaucoma patients showed greater CDR compared to the non-facial PWS and non-glaucoma controls. Additional longitudinal studies are needed to investigate the clinical course of those eyes, whether the risk of developing glaucoma is increased.

Methodology and Rationale for Ophthalmic Examinations in the Seventh and Eighth Korea National Health and Nutrition Examination Surveys (2017–2021)

This report provides a detailed description of the methodology for ophthalmic examinations according to the Korea National Health and Nutrition Examination Survey (KNHANES) VII and VIII (from 2017 to 2021). The KNHANES is a nationwide survey which has been performed since 1998 in representatives of whole Korean population. During the KNHANES VII and VIII, in addition to the ophthalmic questionnaire, intraocular pressure measurement, visual field test, auto refractometry, axial length and optical coherence tomography measurements were included. This new survey will provide not only provide normative and pathologic ophthalmic data including intraocular pressure, refractive error, axial length, visual field and precise measurement of anterior segment, macula and optic nerve with optical coherence tomography, but also a more accurate diagnosis for major adult blindness diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, and other ocular diseases, for the national Korean population.

Methodology and Rationale for Ophthalmic Examinations in the Seventh and Eighth Korea National Health and Nutrition Examination Surveys (2017–2021)

This report provides a detailed description of the methodology for ophthalmic examinations according to the Korea National Health and Nutrition Examination Survey (KNHANES) VII and VIII (from 2017 to 2021). The KNHANES is a nationwide survey which has been performed since 1998 in representatives of whole Korean population. During the KNHANES VII and VIII, in addition to the ophthalmic questionnaire, intraocular pressure measurement, visual field test, auto refractometry, axial length and optical coherence tomography measurements were included. This new survey will provide not only provide normative and pathologic ophthalmic data including intraocular pressure, refractive error, axial length, visual field and precise measurement of anterior segment, macula and optic nerve with optical coherence tomography, but also a more accurate diagnosis for major adult blindness diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, and other ocular diseases, for the national Korean population.

Comparison of Two Combinations of Maximum Medical Therapy for Lowering Intraocular Pressure in Primary Open-angle Glaucoma

Normal-tension Glaucoma Management: A Survey of Glaucoma Sub-specialists in Korea

Purpose@#To investigate the current management patterns of glaucoma subspecialists with regard to normal-tension glaucoma (NTG) in Korea and to determine the effect of the two largest NTG trials on their clinical practice. @*Methods@#A questionnaire survey was sent to glaucoma subspecialist members of the Korean Glaucoma Society. The questionnaire concerned regular practice with respect to NTG and the extent to which it has been influenced by the Collaborative Normal-tension Glaucoma Study and the Low-pressure Glaucoma Treatment Study (LoGTS). @*Results@#A total of 134 glaucoma subspecialists completed the survey, with a response rate of 56%. The survey reported that 88% and 78% of glaucoma subspecialists were familiar with the Collaborative Normal-tension Glaucoma Study and the LoGTS, respectively. With respect to mild or moderate NTG, most of the respondents (87%–91%) tended to treat their patients immediately without waiting for structural or functional progression. Among the respondents, 47 indicated that the LoGTS results—according to which, 20% of the respondents tended to use brimonidine more often—affected their management. The first-choice topical drugs for NTG were prostaglandin analogues (76%), brimonidine (9%), beta-blockers (8%), and topical carbonic anhydrase inhibitor (6%). @*Conclusions@#Regarding mild-to-moderate NTG, Korean glaucoma subspecialists tended to initiate treatment without waiting for further progression. The impact of the LoGTS on NTG management was not dominant in clinical practice in Korea. Prostaglandin analogs are the most frequently selected first-choice drugs for the management of NTG in Korea.

Normal-tension Glaucoma Management: A Survey of Glaucoma Sub-specialists in Korea

Purpose@#To investigate the current management patterns of glaucoma subspecialists with regard to normal-tension glaucoma (NTG) in Korea and to determine the effect of the two largest NTG trials on their clinical practice. @*Methods@#A questionnaire survey was sent to glaucoma subspecialist members of the Korean Glaucoma Society. The questionnaire concerned regular practice with respect to NTG and the extent to which it has been influenced by the Collaborative Normal-tension Glaucoma Study and the Low-pressure Glaucoma Treatment Study (LoGTS). @*Results@#A total of 134 glaucoma subspecialists completed the survey, with a response rate of 56%. The survey reported that 88% and 78% of glaucoma subspecialists were familiar with the Collaborative Normal-tension Glaucoma Study and the LoGTS, respectively. With respect to mild or moderate NTG, most of the respondents (87%–91%) tended to treat their patients immediately without waiting for structural or functional progression. Among the respondents, 47 indicated that the LoGTS results—according to which, 20% of the respondents tended to use brimonidine more often—affected their management. The first-choice topical drugs for NTG were prostaglandin analogues (76%), brimonidine (9%), beta-blockers (8%), and topical carbonic anhydrase inhibitor (6%). @*Conclusions@#Regarding mild-to-moderate NTG, Korean glaucoma subspecialists tended to initiate treatment without waiting for further progression. The impact of the LoGTS on NTG management was not dominant in clinical practice in Korea. Prostaglandin analogs are the most frequently selected first-choice drugs for the management of NTG in Korea.

Comparison of Mean Optic Disc Cup Surface Depth between Primary Open-angle Glaucoma and Glaucoma-like Disc

PURPOSE: Optic nerve head surface depression in patients with glaucoma has been previously reported. We quantitatively compared the mean optic disc cup surface depth between glaucoma-like disc (GLD) patients with large cup-to-disc ratios and primary open-angle glaucoma (POAG) patients. METHODS: A total of 40 eyes of 40 patients with GLD and 40 eyes of 40 patients with POAG were included in this study. All patients had an average cup-to-disc ratio of 0.7–0.8. The optic disc area, mean cup-to-disc ratio, and mean optic disc cup volume were measured using spectral domain optical coherence tomography (Cirrus™ HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA, USA). The mean optic disc cup surface depth was calculated using the formula: (mean optic disc cup volume/[optic disc area × mean cup-to-disc ratio2]) − 200 µm. RESULTS: The mean ages of patients were 61.18 ± 11.83 and 59.65 ± 11.69 years for the GLD and POAG groups, respectively. The average cup-to-disc ratios were 0.74 ± 0.03 and 0.75 ± 0.03 for the GLD and POAG groups, respectively, but no significant difference was observed between the two groups. The mean optic disc cup surface depths were 144.74 ± 82.78 µm and 199.53 ± 90.26 µm for the GLD and POAG groups, respectively, and the difference between the two groups was statistically significant (p = 0.006, t-test). CONCLUSIONS: POAG patients showed a significantly greater mean optic disc cup surface depth compared to GLD patients with a similar mean cup-to-disc ratio. Based on the results of spectral domain optical coherence tomography, confirming the mean optic disc cup surface depth is expected to provide additional information to distinguish GLD from POAG patients.

Clinical Presentation and the Treatment of Glaucoma in Patients with a Facial Port-wine Stain

PURPOSE: To characterize the development of glaucoma, age of glaucoma onset, and treatments for patients with a facial port-wine stain (PWS). METHODS: We performed a retrospective analysis of the medical records of 58 patients (116 eyes) with facial PWS between January 2000 and August 2016. We noted patients' age at the initial examination, cup-to-disc ratio, corneal diameter, occurrence of ocular hypertension, development of glaucoma, age of glaucoma onset, and treatments. We compared the clinical features of eyes that developed glaucoma with those that did not develop glaucoma. Among those eyes with glaucoma, we investigated the differences between eyes that underwent surgery and those that did not undergo surgery. RESULTS: Among the 58 patients with a facial PWS (116 eyes), glaucoma was diagnosed in 38 patients (46 eyes; 39.66%). Of these, 26 patients (27 eyes; 58.69%) underwent glaucoma surgery. PWS-associated glaucoma usually developed by the age of 2 years (85.61%). In all patients, glaucoma developed on the same side of the face as the PWS. Of the 58 patients, 19 (32.76%) showed neurological symptoms, including seizures, developmental delays, intellectual disabilities, or hemiplegia, and 32 (55.17%) were diagnosed with Sturge-Weber syndrome. The mean number of glaucoma surgeries was 1.55 ± 0.93. The initial surgery included trabeculectomy (7 eyes), trabeculotomy (5 eyes), combined trabeculotomy/trabeculectomy (13 eyes), and aqueous drainage device insertion (2 eyes). The mean age at the first surgery was 35.14 ± 50.91 months. In 18 of 27 eyes (66.67%), the postoperative intraocular pressure (IOP) was controlled to below 21 mmHg, but 9 eyes (33.33%) showed elevated IOP and required a reoperation. CONCLUSIONS: PWS can be accompanied by ocular hypertension or glaucoma, so patients require regular ophthalmic examinations. When glaucoma occurs, it often does not respond to medication, making it difficult in some cases to control the IOP, so appropriate glaucoma surgery is necessary.

Long-Term Outcome of Ahmed Valve Implantation Combined with 23-Gauge Vitrectomy in Eyes with Neovascular Glaucoma

PURPOSE: To investigate the surgical outcome of Ahmed glaucoma valve implantation (AVI) combined with 23-gauge vitrectomy in eyes with medically uncontrolled neovascular glaucoma (NVG). METHODS: Thirty six eyes of 35 NVG patients who underwent AVI combined with 23-gauge vitrectomy and have been followed-up at least 6 months after surgery and were retrospectively reviewed. Surgical success was defined as the control of intraocular pressure (IOP) between 6 and 21 mm Hg, irrespective of the use of topical IOP lowering medications. Surgical failure was defined as the failure of IOP control or visual acuity aggravated to no light perception after the surgery. Overall success rate, median survival time, and clinical factors associated with survival time were investigated. RESULTS: The overall success rate was 63.2% after a mean of 34.0 ± 31.7 months postoperative follow-up. The success rate was 83.3% at postoperative 6 months, 72.7% at postoperative 12 months and 63.2% at postoperative 3 years. The underlying retinal diseases were proliferative diabetic retinopathy (PDR; n = 20, 55.5%), central retinal vein occlusion (CRVO; n = 12, 33.3%), ocular ischemic syndrome (n = 2, 5.6%), and other retinal vascular diseases (n = 2, 5.6%). The survival times were significantly shorter in eyes with CRVO (20.2 ± 30.5 months) compared to PDR (33.1 ± 30.8 months), and in phakic eyes (33.1 ± 30.8 months) compared to pseudophakic eyes (37.7 ± 35.4 months) (p < 0.05). In the multivariate analysis, preoperative phakic eyes were significantly associated with a shorter survival time (hazard ratio = 5.626, p = 0.030). CONCLUSIONS: Combined surgery of Ahmed glaucoma valve implantation and 23-gauge vitrectomy showed favorable outcome in the treatment of medically uncontrolled NVG. Preoperative lens status may affect the long-term success rate in such patients.

Long-Term Outcomes of Trabeculectomy in Korean Patients with Juvenile Open-Angle Glaucoma

PURPOSE: To evaluate the outcomes and prognostic factors of trabeculectomy with mitomycin C in Korean patients with juvenile open-angle glaucoma (JOAG). METHODS: A retrospective review was performed on 29 eyes with JOAG who had undergone trabeculectomy between January 2004 and January 2013. Intraocular pressure (IOP) and postoperative complications were monitored at 1 day preoperatively, at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively, and at final follow-up after postoperative 18 months. Surgical success was defined as a final IOP of <21 mm Hg or <80% of preoperative IOP, regardless of the use of anti-glaucoma medication. Prognostic factors for surgical success or failure were analyzed by the Cox proportional hazards model. RESULTS: Mean (+/- standard deviation) age at trabeculectomy was 24.6 (+/- 8.9) years, and mean follow-up period was 24.3 (+/- 20.8) months. The overall success rate was 82.8% at final follow-up. The Kaplan-Meier cumulative probabilities of surgical success were 100% at 1 year, 87.4% at 2 years, and 78.7% at 3 years postoperatively. The Cox proportional hazards model failed to determine any significant factors that were associated with surgical failure. The three most frequent postoperative complications were immediately postoperative hypotony (n = 19, 65.5%), hypotony maculopathy (n = 8, 27.6%), and encapsulated bleb (n = 8, 27.6%), most of which were resolved after a minor procedure or observation. Two of 8 eyes with encapsulated bleb required a second surgery. There were no vision-threatening severe complications. CONCLUSIONS: Trabeculectomy with MMC may be an effective treatment in Korean JOAG patients.

The Efficacy of Amniotic Membrane Graft in the Treatment of Symptomatic Bullous Keratopathy

PURPOSE: To evaluate the efficacy of amniotic membrane (AM) transplantation in symptomatic bullous keratopathy using cryo-preserved or lyophilized AM. METHODS: Eight bullous keratopathic patients, who experienced intractable pain despite medication and the application of a therapeutic lens, underwent permanent AM transplantation with 5 cryo-preserved and 3 lyophilized AMs following removal of epithelium using a trephine. The time to re-epithelization and the subsidence of pain were evaluated retrospectively. RESULTS: Mean follow-up was 252+/-171.0 days. Pain relief and re-epithelization were obtained in all eight patients. The times to complete relief of pain was 32.2+/-22.7 days in patients with cryo-preserved AM transplantations (n=5) and 22.0+/-18.0 days in those with lyophilized AM transplantations (n=3) (p=0.549, Mann-Whitney U test). Respective times to re-epithelization were 25.4+/-20.7 days and 23.0+/-25.2 days (p=0.297). There were no significant differences in the diameter of transplanted AMs between the two groups (7.6+/-0.2 vs. 7.3+/-0.3 mm, p=0.172). CONCLUSIONS: Permanent AM transplantation effectively reduced the intractable pain caused by epithelial bulla. Whether the AM was cryo-preserved or lyophilized did not affect the efficacy of the treatment.

Investigation of the Association between Normal-tension Glaucoma and Single Nucleotide Polymorphisms in Natriuretic Peptide Gene

PURPOSE: The expression of natriuretic peptides in the neural bundles of the anterior portion of the optic nerves and their functions in regulating vessel tone and blood flow may suggest a possible role in the pathogenesis of glaucoma. The purpose of this study was to investigate the association between normal-tension glaucoma and the genetic variations of atrial natriuretic peptide (Nppa) and natriuretic peptide receptor A (Npr1) gene. METHODS: Sixty-seven Korean normal-tension glaucoma (NTG) patients and 100 healthy subjects (as normal controls) were enrolled. DNA from peripheral blood leukocytes was extracted, and the genotypes of five polymorphisms (c.94G>A, c.454T>C, IVS1+16C>T, IVS2+701G>A, and c.-764C>G) in the Nppa gene and one polymorphism (c.1023G>C) in the Npr1 gene were determined using the restriction fragment length polymorphism and the SNaPshot methods. The genotype and allele frequencies of these polymorphisms in patients with NTG and normal controls were compared using the Fisher's exact test and the chi-square test. RESULTS: In both groups, the genotype distributions were in accordance with the Hardy-Weinberg equilibrium. There was no significant difference in the frequency of the Nppa and Npr1 alleles or genotypes in the normal-tension glaucoma group as compared to the control group. CONCLUSIONS: Nppa and Npr1 gene polymorphisms are not associated with normal-tension glaucoma, suggesting that this gene does not have an important role in the pathogenesis of optic neuropathy in this disease.

The Crystallization of Silicone Oil Injected during Complicated Vitrectomy Surgery

PURPOSE: To report three cases of unexpected intraocular foreign bodies which were detected during silicone oil removal procedure following pars planar vitrectomy and silicone oil injection due to the severe vitreoretinal proliferations. METHODS: The medical records of three male patients, aged 61, 40, and 38 years, were reviewed retrospectively. We performed pars planar vitrectomy and silicone oil injection due to submacular hemorrhage with vitreous hemorrhage, tractional retinal detachment with proliferative diabetic retinopathy, and proliferative vitreoretinopathy, respectively. After the retinas were stabilized, we performed silicone oil removal at postoperative 1, 6, and 5 months, respectively. During the silicone oil removal procedure, intraocular foreign bodies were detected and removed with the vitreoretinal forceps. RESULTS: The intraocular foreign bodies were approximately 6 mm x 1 mm in size, transparent, rod-shaped, solid materials. Histopathologic findings didn't show any cellular or intraocular tissue components in and around the foreign bodies. Using electron spectroscopy for chemical analysis, the elemental compositions of the intraocular foreign bodies were determined to be the same as that of the silicone oil that had been previously injected in the eye. We therefore confirmed that those foreign bodies that were removed from the eyes were crystallized remnants of the silicone oil. CONCLUSIONS: Silicone oil can be crystallized after intraocular injection. Therefore, meticulous fundus examination including peripheral fundus is mandatory at the end of the silicone oil removal procedure to prevent any solid silicone foreign bodies from remaining in the eyes. Further investigations are needed to reveal the mechanisms of intraocular crystallization of the silicone oil.

Changes in Astigmatism after Surgical Repair of Epiblepharon or Ptosis: A Vectorial-analytic Approach

PURPOSE: To analyze the changes of astigmatism and keratometric cylinder by using the scalar and vector analysis method in children who had undergone surgery for epiblepharon or ptosis. METHODS: The study subjects were 142 eyes of 79 patients who had undergone surgery for epiblepharon or ptosis. We examined the cycloplegic refractive error and keratometric astigmatism by auto-refractometry before and 2 months after surgery. Astigmatic changes were analyzed through the scalar and vector analysis method. RESULTS: The mean age of the patients was 5.27+/-2.18 years of age, and the male to female ratio was 35: 44. There were 98 eyes of 49 patients in the epiblepharon surgery group, 28 eyes of 22 patients in the ptosis surgery group, and 16 eyes of 8 patients in the epiblepharon and ptosis surgery (combined surgery) group. The epiblepharon surgery group demonstrated a decrease in with-the-rule astigmatism, and the changes in magnitude (p<0.001) and vector (p<0.05) of keratometric cylinder were statistically significant. The ptosis surgery group demonstrated an increase in with-the-rule astigmatism and the changes in magnitude and vector of astigmatism were statistically significant (both p<0.01). The combined surgery group demonstrated an increase in with-the-rule astigmatism and the changes in vector of astigmatism and magnitude of keratometric cylinder were statistically significant (both p<0.05). CONCLUSIONS: Our results showed significant astigmatic change in eyes that underwent surgery for epiblepharon or ptosis. Therefore, careful cycloplegic refraction is necessary after epiblepharon or ptosis surgery.

The Effect of Amniotic Membrane Transplantation on the Treatment of Necrotizing Scleritis after Pterygium Excision

PURPOSE: To investigate the efficacy of amniotic membrane transplantation (AMT) in patients who were diagnosed with necrotizing scleritis after pterygium excision and who were refractory to systemic corticosteroid and immunosuppressive therapy. METHODS: Six patients who had persistent scleral melting with systemic corticosteroid or immunosuppressive agents underwent double AMT as a permanent patch graft and temporary overlying barrier. Postoperatively, the symptom improvements, reepithelization times and visual acuity changes were evaluated. RESULTS: Choroidal detachment was detected in two patients preoperatively. In all patients, ocular pain improved at 4.7 +/- 3.1 days, and reepithelization of the scleral lesions was completed at 13.2 +/- 8.1 days postoperatively. Choroidal detachment in two patients disappeared at postoperative 2 and 8 days. Complete remission was found in 5 of the 6 eyes (83.3%). One eye which achieved full epithelization in the necrotic area experienced recurrent nodular scleritis in another quadrant, resulting in remission after changing the regimen of immunosuppressive agents. Mean values of initial and final visual acuities were 0.898 logMAR and 0.428 logMAR, respectively, and the visual acuities improved in all patients. CONCLUSIONS: AMT is effective in promoting reepithelization of the necrotic area, resulting in complete remission of necrotizing scleritis in patients who were refractory to systemic corticosteroid or immunosuppressive therapy.

Argon Laser Ablation of Conjunctival Nevus

PURPOSE: To evaluate the efficacy of argon laser in the ablation of benign conjunctival pigmented nevi. METHODS: We conducted a prospective, observational case study, on a series of argon laser ablations of conjunctival pigmented nevi, in 30 eyes of 28 patients. Laser ablation was applied directly to the conjunctival pigmented nevus in all patients. The mean age of the patients was 33.0 +/- 9.3 years old, and the male to female ratio was 3: 25. All patients were followed up over a period of at least 6 months. RESULTS: The mean size of the conjunctival lesions was 3.9 X 2.8 mm. In all patients, the conjunctival lesions to which the argon laser was applied disappeared almost completely within two days after treatment. No lesion recurrence was detected in any patient during the follow-up period, nor were there any conjunctival scars or conjunctival injection. All patients were satisfied with the results of the procedure. CONCLUSIONS: Argon laser ablation of conjunctival pigmented nevi resulted in uniformly excellent clinical outcomes. Therefore, this study concludes that argon laser ablation is a safe and effective modality for the treatment of benign conjunctival nevi, and that this method is capable of replacing the classical surgical procedure.