Juvenile Primary Open-angle Glaucoma Research Articles

Juvenile primary open-angle glaucoma and keratoconus

Juvenile primary open-angle glaucoma and keratoconus

Comparison between choroidal thickness in normal and glaucomatous eyes using spectral-domain optical coherence tomography

Purpose The aim of this study was to compare choroidal thickness in healthy and glaucomatous eyes using spectral-domain optical coherence tomography. Patients and methods This prospective study was carried out on patients recruited from the Department of Ophthalmology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt, from April 2015 to April 2016. Informed consent was obtained from all participants. The studied participants were divided into two groups: group 1, which included 100 healthy eyes with normal intraocular pressure, and group 2, which included 100 juvenile and adult-onset primary open-angle glaucomatous eyes. All participants had undergone high-definition raster scanning using spectral-domain optical coherence tomography (Cirrus HD-OCT Model 4000) (software, version 6.0) with frame enhancement software. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction in 11 points. The centre of the fovea (F0) plus five temporal points separated by 500 μm (T0.5, T1.0, T1.5, T2.0 and T2.5) and five nasal points separated by 500 μm (N0.5, N1.0, N1.5, N2.0 and N 2.5) was studied. Statistical analysis of the results was performed using the unpaired t-test. Results Choroidal thickness in group 2 was significantly less than that in group 1 in all studied points with the exception of T0.5 and subfoveal (F0) choroidal thickness. Conclusion The findings of the present study confirmed that choroidal thickness, except for the subfoveal choroidal thickness and 500 μm temporal to the fovea, is significantly less in juvenile and adult-onset primary open-angle glaucoma eyes compared with age-matched normal eyes. Whether this finding represents a risk factor or a consequence of the disease requires further investigations.

Agreement in identification of glaucomatous progression between the optic disc photography and Heidelberg retina tomography in young glaucomatous patients.

To evaluate concordance between the clinical assessment of glaucomatous progression of the optic disc photography and progression identified by Heidelberg Retina Tomograph (HRT) in patients with suspected primary juvenile open angle glaucoma (JOAG). Optic disc photographs and corresponding HRT II series were reviewed. Optic disc changes between first and final photographs were noted as well as progression identified by HRT topographic change analysis (TCA) and rim area regression line (RARL) Agreement between progression indentified by photography and HRT methods was assessed. Progression, determined from optic disc photographs by consensus assessment was used as the reference standard. A total of 31 patients (59 eyes) with suspected JOAG were studied. Agreement for progression/no progression between TCA and photography was obtained in 4 progressing eyes and 38 stable eyes (71.19%, k=0.11). Agreement for progression/no progression between RARL and photography was detected in 5 progressing eyes and in 34 stable eyes (66.10%, k=0.15). The number of HRT per patient was statistically higher in the progressing group (P=0.034). Agreement for detection of longitudinal changes between photography and HRT analysis was poor. One way to improve the chance of discovery of the progression could be increasing the number of HRT examinations.

Outcomes of trabeculectomy in juvenile open angle glaucoma

Purpose:This study was aimed at reporting the outcomes of trabeculectomy in primary juvenile open angle glaucoma (JOAG).Design:This study was a retrospective noncomparative case series.Materials and Methods:We included 60 eyes of 41 JOAG patients who underwent primary trabeculectomy without mitomycin-C (MMC) between 1995 and 2007. The primary outcome was success, defined as complete, if intraocular pressure (IOP) was >5 and ≤21 mmHg without medications or qualified if IOP was >5 and ≤21 mmHg with or without antiglaucoma medications. Secondary outcome measures were mean and percentage IOP reduction, complications, and risk factors for the failure of trabeculectomy.Results:The mean (±standard deviation) age at presentation was 24.1 ± 6.8 years (range, 12–35). Mean follow-up was 67 ± 41 months (range, 12–156). At 1 year, the probability of complete success was 92% (n = 56, 95% CI: 81–96%), at 3 years it was 89% (n = 47, 95% CI: 78–95%), and at the end of 5 years, it was 80% (n = 34, 95% CI: 65–89%). The probability of qualified success was 100% (n = 60) at 1 year, 98% (n = 51, 95% CI: 87–100%) at 3 years, and 96% (n = 36, 95% CI: 84–99%) at the end of 5 years. The mean IOP reduced from 35 ± 10 to 13 ± 2.5 mmHg (P < 0.001) after trabeculectomy. There was no serious postoperative complication. Young age was the only significant risk factor associated with the failure (odds ratio = 0.89, P = 0.03).Conclusion:Primary trabeculectomy without MMC has good success rates in JOAG.

Determinants of severity at presentation among young patients with early onset glaucoma

Aim:The aim of this study was to evaluate the clinical, socio-economic, and demographic factors associated with the severity at presentation among juvenile primary open angle glaucoma (JOAG) patients.Materials and Methods:Age at diagnosis, family history, baseline intraocular pressure (IOP), access to health-care, socio-economic status, and glaucoma awareness among 80 unrelated JOAG patients presenting between 10 years and 40 years of age were analyzed for their association with the severity at presentation. Severity at presentation was graded based on worse eye visual field using the advanced glaucoma intervention study score and on binocular visual field defects at presentation.Results:Patients with a positive family history presented 4 years earlier (P = 0.045, confidence interval [CI]: 0.09-8.8) compared to those without a family history. Lower socio-economic status (Odds ratio [OR] 5.7, P = 0.01, CI: 1.5-22), and higher baseline IOP (OR 7, P = 0.003, CI: 1.9-26) were associated with severe glaucomatous visual field defect at presentation. A negative family history was associated with a 10 times likelihood of presenting with a severe glaucomatous field defect (OR 0.1, P = 0.007, CI: 0-0.5).Conclusions:Clinical, socio-economic, and demographic factors are contributory to the severity at presentation among young patients with early onset glaucoma. Presence of a family history is associated with an earlier presentation among these patients and a reduced risk of the severe presentation.

Visual field progression outcomes in glaucoma subtypes

To determine whether glaucoma subtype is an independent risk factor for visual field (VF) progression. We reviewed the charts of glaucoma suspects and glaucoma patients seen in a referral practice between 1999 and 2009. Automated pointwise linear regression analysis determined the rates of VF change. A progression endpoint was determined when two or more adjacent test locations in the same hemifield showed a threshold sensitivity decline at a rate of ≥1.0 dB/year with p < 0.01. We included 841 eyes (841 patients; mean age, 64.1 ± 12.6 years; mean number of VF tests, 10.8 ± 2.8; mean follow-up, 6.4 ± 1.7 years). The glaucomatous group consisted of angle-closure glaucoma (76 eyes), juvenile primary open-angle glaucoma (37 eyes), normal-tension glaucoma (81 eyes), pigmentary glaucoma (34 eyes), primary open-angle glaucoma (275 eyes) and exfoliative glaucoma (XFG, 84 eyes). Normal-tension glaucoma eyes were more likely to present with beta-zone parapapillary atrophy and disc haemorrhage (p < 0.01). Exfoliative glaucoma eyes had the fastest rates of global VF change (-0.65 dB/year), as well as the highest mean, fluctuation, and peak intraocular pressure during follow-up (16.5, 3.0 and 22.0 mmHg, respectively) and reached a progression endpoint more frequently (40%). After adjusting for all covariates, including the glaucoma phenotype, there was no difference among groups regarding global rates of VF change and the risk of reaching a progression endpoint. Despite different clinical features, epidemiology and genetics, glaucoma phenotype is not an independent risk factor for VF progression. Rather, variations in well-known, reported risk factors remain important disease parameters that affect progression.

Effect of 2% dorzolamide on retinal blood flow: a study on juvenile primary open‐angle glaucoma patients already receiving 0.5% timolol

To investigate whether dorzolamide modifies peripapillary retinal haemodynamics in juvenile primary open-angle glaucoma (JPOAG) patients treated with timolol. In 40 JPOAG subjects, before and after dorzolamide coadministration with timolol, the following examinations were achieved: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), heart rate (HR), visual field and retinal flowmetry. Adjunctive therapy with dorzolamide induced the following modifications: IOP reduction [1.75 mmHg, 95% confidence interval (CI) 1.23, 2.26; P < 0.05], OPP increase (5.09 mmHg, 95% CI 2.97, 7.20; P < 0.02) and retinal blood flow improvement (35.0 arbitrary units, 95% CI 12.20, 57.80; P < 0.03). BP, HR and visual field indices did not change. Dorzolamide, in association or in fixed combination with timolol, significantly improves retinal blood flow in JPOAG patients.

Assessment of Retinal Nerve Fiber Layer Using Optical Coherence Tomography and Scanning Laser Polarimetry in Progressive Glaucomatous Optic Neuropathy

To describe a case of progressive glaucomatous optic neuropathy using scanning laser polarimetry with fixed (SLP-FCC) and variable corneal compensation (SLP-VCC) and optical coherence tomography (OCT). Observational case report. A 21-year-old male with juvenile primary open-angle glaucoma developed progression because of noncompliance with therapy. The patient underwent dilated stereoscopic examination and photography of the optic disk, standard automated perimetry (SAP), OCT, and SLP imaging with FCC and VCC at the baseline examination and after four years of follow-up. Optic disk, retinal nerve fiber layer (RNFL) atrophy, and SAP progression was observed. Reduction in mean RNFL thickness (average, superior, inferior) was 18, 18, and 27 microns (OCT); 22, 40, and 17 microns (SLP-FCC); and 6, 12, and 12 microns (SLP-VCC), respectively. This case demonstrates that digital imaging of the peripapillary RNFL is capable of documentation and measurement of progressive glaucomatous RNFL atrophy.

Trabeculectomy with Mitomycin C versus Trabeculectomy Alone for Juvenile Primary Open-Angle Glaucoma

Purpose: We compare the intermediate-term outcome of initial trabeculectomy with adjunctive mitomycin C use versus initial trabeculectomy alone for juvenile primary open-angle glaucoma. Methods: This retrospective consecutive analysis included 44 eyes from 36 patients with juvenile primary-open angle glaucoma, all of whom underwent either initial trabeculectomy with adjunctive mitomycin C use (15 eyes) or initial trabeculectomy alone without mitomycin C use (29 eyes). We compared the success rate and complications between the two groups in a three-year follow-up period following surgery. Results: Three years subsequent to surgery, the cumulative success probability was 73% for the mitomycin C group and 68% for the control group, there being no real difference between the two groups (p = 0.89). A greater incidence of hypotony maculopathy was found amongst the mitomycin C group than was the case for the control group (20 versus 0%, respectively, p = 0.034). A lower intraocular pressure amongst the mitomycin C group was noted as compared with the control group (10.8 ± 3.0 versus 13.3 ± 3.8 mm Hg, respectively, p = 0.017) amongst the successfully treated patients. Conclusions: Despite the lower intraocular pressure level for the successfully treated patients from the trabeculectomy with mitomycin C group, and a greater incidence of resultant hypotony maculopathy for this group as compared with the trabeculectomy alone group, there appeared to be no significant difference in the cumulative success probability for this group as compared with the trabeculectomy alone group. Therefore, we caution against the use of an initial trabeculectomy with mitomycin C for juvenile primary open-angle glaucoma.

Comparisons of Risk Factors and Visual Field Changes between Juvenile-Onset and Late-Onset Primary Open-Angle Glaucoma

Purpose: To identify the differences in risk factors and visual field (VF) changes between juvenile primary open-angle glaucoma (JOAG) and late-onset chronic open-angle glaucoma (COAG). Methods: The demographic and presenting clinical data of 27 JOAG and 30 COAG patients were retrospectively reviewed. Comparisons between the two groups were performed using Mann-Whitney U test, Wilcoxon signed-rank test, and Fisher’s exact test. Results: A family history of glaucoma (37%) and a history of steroid usage (14.8%) were identified in JOAG patients only. The JOAG patients had a longer axial length (p < 0.001) and more often a myopic refractive state (p < 0.001) than the COAG patients. Patients with COAG showed a deeper (p = 0.016) and a more extensive (p = 0.008) defect in the superior than in the inferior hemifield, as well as a deeper (p = 0.016) and a more extensive (p = 0.001) defect in the superior than in the inferior arcuate area, while JOAG patients showed symmetric VF defects between the superior and inferior hemifields. Purely diffuse VF depression is more common in JOAG than in COAG patients (p = 0.03). Conclusions: JOAG patients demonstrated more axial myopic changes than patients with COAG as well as a pattern of superior-inferior symmetric VF defects. Axial myopia may play a critical role in the pathogenesis of JOAG.

Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma

PURPOSE: To screen a population with primary open-angle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC). METHODS: Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary open-angle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites. RESULTS: In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary open-angle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). In families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%). CONCLUSIONS: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser are likely to play roles that cause or contribute to the etiology of autosomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed.

Regulation of human myocilin/TIGR gene transcription in trabecular meshwork cells and astrocytes: role of upstream stimulatory factor.

Mutations in the myocilin (MYOC)/TIGR gene are responsible for autosomal-dominant juvenile primary open-angle glaucoma (POAG). In patients with non-autosomal-dominant POAG, such mutations are rare, but the expression of MYOC/TIGR in the trabecular meshwork (TM) of the eye is considerably higher than in normals. We performed transfection, DNAse I footprinting, mutagenesis and electrophoretic mobility shift assays (EMSA) to identify elements responsible for the basal transcription of MYOC/TIGR in TM cells and astrocytes. DNAse I footprinting experiments of the human MYOC/TIGR promoter showed a major protected area between nt -106 to -77, which was not conserved in the homologous region of the mouse myoc/tigr promoter. In addition, the TATA-box was protected, as well as at least three downstream sites, including an AP-1-like sequence. Deletion of the -106 to -77 region caused a substantial loss of functional promotor activity in all cell types. Site-directed mutagenesis and EMSA experiments revealed the presence of two regulatory elements in the -106 to -77 region. Each of these cis-elements is essential for minimal promoter activity. The 5'-half of the region contains a sequence with similarities to NF-kappaB-related sites, however, binding of NF-kappaB could not be confirmed by EMSA. The 3'-half contains a canonical E-box sequence. EMSA experiments showed that the upstream regulatory factor (USF) was binding to the E-box sequence and that the binding can be supershifted by specific antibodies. Several DNA-protein binding elements contribute to a transcription of MYOC/TIGR, and USF is critically required for its basal transcription in trabecular meshwork cells and astrocytes.

Optic disc morphology in juvenile primary open-angle glaucoma.

The aim of the study was to evaluate whether, in primary open-angle glaucoma (POAG), patients younger than 40 years differ in optic disc morphology from patients older than 40 years. Out of a total group of 419 patients with POAG, we formed and compared two subgroups, one consisting of 37 patients with an age of less than 40 years, the other composed of 382 patients with an age equal to or more than 40 years. Both subgroups were matched for neuroretinal rim area. We examined the optic disc morphometrically using stereo disc photographs. The younger subgroup, as compared to the older subgroup, showed deeper and steeper optic disc cupping, concentric emaciation of the neuroretinal rim, a significantly smaller area of parapapillary atrophy, and significantly higher maximal and minimal intraocular pressure measurements (P < 0.001). The size and shape of the optic disc and the diameter of the retinal vessels at the optic disc border did not vary significantly. In POAG, patients younger than 40 years differ in optic disc morphology from patients older than 40 years. The younger patients with POAG have high minimal and maximal intraocular pressure readings and an optic disc morphology with deep and steep cupping, concentric loss of neuroretinal rim, and an almost unremarkable parapapillary atrophy. POAG in patients under 40 represents chronic high-pressure open-angle glaucoma with mainly diffuse optic nerve damage.

Reduced trabecular meshwork height in juvenile primary open-angle glaucoma.

To compare trabecular meshwork height in a series of patients with juvenile primary open-angle glaucoma (JPOAG) with that in normal control patients. Ultrasound biomicroscopy and A-scan biometry were performed on 16 eyes with JPOAG and 24 normal eyes. A radial, perpendicular image in the horizontal temporal meridian detailing the line of Schwalbe, scleral spur, and angle anatomy was obtained for each eye by a single examiner. Trabecular meshwork height was defined as the distance from the scleral spur to the Schwalbe line. Mean patient age (P = .85, t test), refractive error (P = .68), sex distribution (P = .26, Fisher exact test) and axial length (P = .39) were similar between the groups. Mean +/- SE trabecular meshwork heights were 0.36 +/- 0.03 mm (range, 0.19-0.53 mm) for JPOAG and 0.58 +/- 0.02 mm (range, 0.40-0.80 mm) for controls (P < .001). Eyes with greater axial length tended to have larger trabecular meshworks in both groups (P = .012, multivariate regression). A trabecular meshwork height-axial length ratio of 0.021 or less was associated with a significantly increased risk for JPOAG being present (odds ratio, 57; 95% confidence interval, 6.0-541). The trabecular meshwork is smaller in eyes with JPOAG compared with that in normal eyes. This finding suggests a structural abnormality that may underlie the reduced outflow.

Trabeculotomy in Juvenile Primary Open-Angle Glaucoma

ABSTRACT Long-term results of trabeculotomy in juvenile primary open-angle glaucoma (JPOAG) were investigated based on a follow-up study of 16 eyes in 11 patients, diagnosed when they were between 10 and 46 years old. Preoperative visual field defects were found in 75% (12/16) of the eyes. After a mean follow up of 7 years (range, 1 to 18 years), 88% (14/16) of the eyes had an intraocular pressure (IOP) of 21 mm Hg or less (peak pressure at diurnal curves). Nine of these were receiving no medical treatment and five were being treated with beta-blockers and/or dipivefrin. The best results were in the younger patients; the success rate of those under age 40 years was 100%. After normalization of IOP, visual field testing showed no progression in defects. We conclude that trabeculotomy rather than filtering surgery should be used to treat JPOAG, because the success rate of filtering surgery decreases with decreasing age. Also, the good functional results achieved in these patients after normalization of IOP may indicate that ocular hypertension is the only risk factor in JPOAG.

Initial 5-Fluorouracil Trabeculectomy in Young Patients

The effectiveness of initial trabeculectomy with adjunctive 5-fluorouracil (5-FU) for uncomplicated glaucoma in patients age 40 years or younger at the time of surgery was evaluated retrospectively in a consecutive series of 20 eyes of 20 patients. Fifteen patients had juvenile primary open-angle glaucoma, 4 had pigmentary glaucoma, and 1 had glaucoma associated with angle recession. Mean patient age was 26.8 +/- 9.7 years (range, 13 to 40 years) at the time of surgery. The mean total 5-FU dose administered was 27.8 +/- 8.8 mg (range, 15 to 45 mg). The intraocular pressure (IOP) decreased from 34.4 +/- 11.5 mmHg preoperatively to 10.5 +/- 4.0 mmHg postoperatively after a mean follow-up of 31.1 +/- 17.3 months (range, 11.5 to 70 months). Nineteen eyes (95%) had a postoperative IOP of 20 mmHg or less without pressure-lowering medications. One patient required additional medical therapy to control the IOP. Complications included bleb-related endophthalmitis (2 eyes) and hypotony maculopathy (1 eye).

Juvenile Glaucoma, Race, and Refraction

Of 68 patients who presented between the ages of 10 and 35 years with elevated intraocular pressure, 25 were classified as juvenile ocular hypertension and 43 as juvenile primary open-angle glaucoma. Blacks constituted a greater proportion of the primary open-angle glaucoma patients (47%) than of the ocular hypertensives (20%) and in both groups presented at younger ages than did whites. Myopia was present in 59% of the ocular hypertensives and 73% of the primary open-angle glaucoma patients, of whom 39% had more than 6 diopters of myopia. All eyes of black patients with more than 3 diopters of myopia had glaucomatous defects compared with 52% of such eyes of white patients. Our data suggest that myopia is strongly associated with juvenile open-angle glaucoma and that young black patients with elevated intraocular pressure, especially when myopic, are more susceptible to glaucomatous damage than are whites.

JUVENILE GLAUCOMA IS MORE DAMAGING IN BLACKS.

Juvenile primary open-angle glaucoma, which affects patients aged 10 to 35, is more severe than the adult form of glaucoma. This study of 68 young patients presenting with elevated intraocular pressure …