Progressive Visual Field Loss Research Articles

Relationship between central corneal thickness and progression of visual field loss in patients with open-angle glaucoma

ObjectiveTo determine whether a relationship exists between central corneal thickness (CCT) and visual field (VF) progression in treated patients with open-angle glaucoma and asymmetric corneal thickness. DesignRetrospective chart review. ParticipantsWe studied 100 charts of patients with open-angle glaucoma and also bilateral CCT and VF data. MethodsCharts from 2 glaucoma subspecialty practices were reviewed. The CCT and the rate of progression and event analysis of visual field data were assessed in all subjects. Subanalysis was performed for subjects whose CCT asymmetry was ≥ 16 μm. ResultsThe mean CCT was 544 ± 40 μm OD and 541 ± 40 μm OS. The mean CCT difference between fellow eyes was 15 ± 11 μm (range, 1 to 52 μm). There was no significant intrasubject difference in the mean deviation (MD) and the pattern standard deviation (PSD) (p =0.917 and p = 0.704, respectively; paired t test). The more advanced VF MDs and PSDs were found in the thin eyes of 47 and 50 subjects, respectively (p = 0.459 and p = 0.317, respectively; χ2). Of the 65 subjects whose visual field indexes were available, 34 had the more rapid visual field index rates of progression in the thin eye (p = 0.400; χ2). Of the 27 subjects for whom event analysis was available, 15 had the worse progression category in the thin eye (p = 0.453, χ2). Subgroup analysis of 48 subjects with ≥ 16 μm CCT asymmetry did not find any significant difference in analyses of field progression between fellow eyes. ConclusionsNo relationship was found between CCT and VF loss in treated patients with primary open-angle glaucoma or normal-tension glaucoma with asymmetrical CCT. Specifically, the thin eye did not have the more advanced VF loss or more rapid VF progression.

Republished: Glaucoma: a systemic condition?

Primary open-angle glaucoma (POAG) is an optic neuropathy associated with the loss of retinal ganglion cells. The pathophysiology of the disease is incompletely understood. Increased intraocular pressure (IOP) is the...

Recent clinical pearls from clinical trials in glaucoma

Over the past several years, numerous clinical trials in glaucoma have contributed to our understanding of the medical and surgical treatment of the disease. The goal of this review is to summarize the findings and conclusions of what the authors feel are the key clinical trials in glaucoma. One of the major findings of Low-Pressure Glaucoma Treatment study was that patients randomized to the brimonidine group were statistically less likely to have progressive visual field loss than those randomized to the timolol group, even though there was no significant difference between the intraocular pressure (IOP)-lowering effect of these two drugs. The Ocular Hypertension Treatment Study has effectively demonstrated that patients with ocular hypertension should be risk stratified prior to initiation of treatment and that it appears to be relatively safe to delay treatment in low-risk patients. The 3-year canaloplasty study demonstrates the long-term safety and efficacy of this surgery. However, it also demonstrates that canaloplasty can deliver a modest IOP reduction and therefore is likely more suited for patients with mild damage and a higher target IOP. The 1-year results from the Ahmed Baerveldt Comparison Study do not demonstrate a clear superiority of one implant over the other. These findings are consistent with prior retrospective studies in the literature. These four studies have furthered our understanding of the field of glaucoma and provided key insights into the medical and surgical management of patients with this complex disease.

Improved Prediction of Rates of Visual Field Loss in Glaucoma Using Empirical Bayes Estimates of Slopes of Change

To describe and test a new methodology for estimation of rates of progressive visual field loss in glaucoma. This observational cohort study enrolled 643 eyes of 368 patients recruited from the Diagnostic Innovations in Glaucoma Study, followed for an average of 6.5±2.0 years. The visual field index was used to evaluate degree of visual field loss in standard automated perimetry. Growth mixture models were used to evaluate visual field index changes over time. Empirical Bayes estimates of best linear unbiased predictions (BLUPs) were used to obtain slopes of change based on the first 5 visual fields for each eye. These slopes were then used to predict future observations. The same procedure was done for ordinary least squares (OLS) estimates. The mean square error of the predictions was used to compare the predictive performance of the different methods. The growth mixture model successfully identified subpopulations of nonprogressors, slow, moderate, and fast progressors. The mean square error was significantly higher for OLS compared with the BLUP method (32.3 vs 13.9, respectively; P<0.001), indicating a better performance of the BLUP method to predict future observations. The benefit of BLUP predictions was especially evident in eyes with moderate and fast rates of change. Empirical Bayes estimates of rates of change performed significantly better than the commonly used technique of OLS regression in predicting future observations. Use of BLUP estimates should be considered when evaluating rates of functional change in glaucoma and predicting future impairment from the disease.

Pharmakologische Ansätze in der Therapie erblicher Netzhautdegenerationen

This article reviews the current pharmacological strategies to treat inherited retinal degeneration. To date there is no causal therapy despite growing knowledge of the particular pathomechanisms. However, treatment is available for complications, such as cystic macular changes and cystoid macular edema. To reduce retinal thickness systemic or topical carboanhydrase inhibitors can be applied and in rare cases combined with steroids when indicated, however reduction of retinal thickness is not always accompanied by improvement of visual acuity. Regular follow-up with optical coherence tomography is required. In some cases, potentially neuroprotective agents (valproic acid, ciliary neurotrophic factor and Ca(2+ ) channel inhibitors) or food supplementation (vitamin A, lutein, synthetic retinoids and decosahexaenoic acid) may have a positive impact on disease progression (e.g. reduction in progression of visual field loss or individual electrophysiological parameters). However, beneficial effects and side effects, e.g. of vitamin A substitution, depend not only on the disease phenotype (such as retinitis pigmentosa) but also on the actual genotype. Furthermore, no data are available regarding the application of pharmaceuticals in the pediatric population.

Correlation of the rate of progression of visual field loss between Guided Progression Analysis (GPA II) and PeriDataTM program in glaucoma patients: Pilot study

AbstractPurpose To assess the correlation of progression rate measured by GPAII using visual field index (VFI%) and PeriDataTM employing functional equivalent score (FES) in glaucoma patients.Methods Retrospective, observational study including 54 eyes of 37 medically treated glaucoma patients with at least 5 reliable visual field examinations in minimum 2 years. Only patients with a negative rate of progression with VFI were taken into account to calculate their rate of progression and loss of FES. Patients who underwent filtering surgery or laser trabeculoplasty during the follow‐up period were excluded.Results Mean age was 75.7 ±13.4 yrs. the patients performed their visual field with Humphrey standard automated perimeter (Sita Standard 24‐2). The mean follow‐up was 7.5 ± 2.5 yrs. The mean of progression by GPA (%/year) and PeriData FES index (%/year) were: ‐2.0 ± 2.2 (range= ‐10.6 to ‐0.2 per year) and ‐3.18 ± 2.5 (range: ‐9.3 to 2.8 per year) respectively. There was an excellent correlation between GPAII index VFI% loss per year and PeriData FES loss per year (&lt;0.001) for the total group. In contrary when the group was limited to low‐ moderate progressors (VFI% loss per year ≥ ‐2), there was no correlation between the two different indexes.Conclusion In this study we couldn't find any correlation between VFI% and FES% in the clinically low to moderate visual field progression.

Association between intraocular pressure and adherence: is there one?

Sir, The paper by Ajit et al1 that was recently published in Eye described a new methodology of graphically presenting adherence data, using an electronic dosing monitor. The concept of using such a device to provide meaningful, graphical information is potentially favourable to the clinician in identifying patterns of adherence. However, the idea of collecting this information for all patients is probably unrealistic and unlikely to be cost-effective. Lowering intraocular pressure (IOP) to reduce or halt the progression of visual field loss is the only currently available intervention for patients with glaucoma. Measuring IOP to assess efficacy has been standard practice ever since topical anti-glaucoma therapy was commenced. If a therapeutic regimen is adhered to, a reduction in IOP would be expected on repeat measurement a priori. Theoretically, therapeutic outcome would be both an objective and a practical measure of adherence. However, to date there is no consistent evidence of a relationship between adherence and IOP.2 Failure to identify such a relationship could be explained by the lack of a quantified correlation, or could be attributed to the methodological quality of the studies examining such a correlation being poor. However, it is more likely that the complexities of assessing the level of IOP due to individual differences (types of glaucoma and diurnal variance), together with regression to the mean, lead to ‘noisy data'. The methodology used by Ajit et al1 stated that 100 patients at their initial interview had their IOP recorded. However, no further discussion of the IOP data was done in the paper. Assuming that Ajit et al had the intention of collecting IOP data to study any relationship between IOP and adherence, it would be interesting if their findings could be published, particularly given the potential value to the glaucoma clinician of learning how IOP measures might correlate with adherence.

Automated alternation flicker for the detection of optic disc haemorrhages

Optic disc haemorrhages are associated with active glaucomatous neurodegeneration and ongoing visual field loss. We sought to determine whether automated alternation flicker enhances the detection of disc haemorrhages in serial images from patients with glaucoma when compared to side-by-side photographic evaluation and single-image display. Serial sets of optic nerve photographs of 394 eyes from 234 patients followed for glaucoma at the authors' institutions were included in this study. Eyes with disc haemorrhages were graded for difficulty level and randomized along with nondisc haemorrhage control images into one of three presentation groups (automated alternation flicker, side-by-side or single image). Seven graders viewed all images and assessed for the presence or absence of disc haemorrhages. The sensitivity of automated alternation flicker for disc haemorrhage detection (0.878) was higher than side-by-side (0.705; p = 0.002) and single photographs (0.757; p = 0.01). There was no specificity difference between pairs of presentation groups (all p ≥ 0.7). Automated alternation flicker was a more sensitive method for disc haemorrhage detection than the current clinical standards and may have an important role in the management of glaucoma.

Evidence for a Novel Autosomal Dominant Retinitis Pigmentosa Linked to Chromosome 1p22.1-q12 in a Chinese Family

Purpose: To identify the causative genetic locus in a Chinese autosomal dominant retinitis pigmentosa (adRP) family that contained seven affected members in three generations.Methods: After clinical diagnosis and exclusion of all mapped genes and loci, the SLINK program was used to simulate the maximum logarithm of the likelihood ratio (LOD) score for a linkage study in this small family. A genome-wide scan was performed using microsatellite markers at 10 cM intervals. Two-point and multipoint LOD scores were calculated, and haplotypes were constructed.Results: The H11 family clinical presentation included an early onset of night blindness, a progressive loss of the peripheral visual field, typical retinitis pigmentosa (RP) fundus changes, and a cataract complication. A maximum two-point LOD score of 2.54 (θ = 0) was found at markers D1S2739, D1S457, D1S187, D1S189, and D1S305, and multipoint linkage analysis yielded a maximum LOD score of 2.54 for marker D1S187. These LOD scores were the closest to the maximum simulated LOD score. Haplotype analysis revealed that this form of adRP segregates with a 38.25 cM region that spanned 50 Mb on chromosome 1p22.1-q12.Conclusions: Although this locus overlaps the RP19 locus caused by mutations in ABCA4 and the RP32 locus, both are inherited in an autosomal recessive mode rather than the autosomal dominant mode of inheritance found in the H11 family. The identification of this potential new locus for adRP further confirms the high level of heterogeneity for RP.

Glaucoma Surgery

Glaucoma is a potentially blinding condition that cannot be easily defined. There are various types of glaucoma which may vary in symptoms from none at all to sudden pain and redness. There is a characteristic optic neuropathy, or damage to the optic nerve, which results in progressive loss of visual field. The most important risk factor is an increase in the intraocular pressure (IOP) secondary to a reduction in the drainage of aqueous fluid from the drainage pathways in the eye, the filtration angle (Kanski 2007, Allingham et al 2011).

Complex genetic mechanisms in glaucoma: An overview

Glaucomas comprise a group of hereditary optic neuropathies characterized by progressive and irreversible visual field loss and damage to the optic nerve head. It is a complex disease with multiple molecular mechanisms underlying its pathogenesis. Genetic heterogeneity is the hallmark of all glaucomas and multiple chromosomal loci have been linked to the disease, but only a few genes have been characterized, viz. myocilin (MYOC), optineurin (OPTN), WDR36 and neurotrophin-4 (NTF4) in primary open angle glaucoma (POAG) and CYP1B1 and LTBP2 in congenital and developmental glaucomas. Case-control-based association studies on candidate genes involved in different stages of glaucoma pathophysiology have indicated a very limited involvement. The complex mechanisms leading to glaucoma pathogenesis indicate that it could be attributed to multiple genes with varying magnitudes of effect. In this review, we provide an appraisal of the various efforts in unraveling the molecular mystery in glaucoma and also some future directions based on the available scientific knowledge and technological developments.

The Relationship between Intraocular Pressure Reduction and Rates of Progressive Visual Field Loss in Eyes with Optic Disc Hemorrhage

The Relationship between Intraocular Pressure Reduction and Rates of Progressive Visual Field Loss in Eyes with Optic Disc Hemorrhage

A Review of Current Technology Used in Evaluating Visual Function in Glaucoma

Glaucoma is a blinding disease associated with characteristic progressive optic nerve damage and visual field loss. Visual field testing in the form of automated perimetry is critical in the clinical diagnosis and monitoring of glaucoma. Functional tests can also be powerful research tools in clinical trials and in the field of neuroprotection. Standard automated perimetry (SAP) commonly used today, however, has its limitations. Early diagnosis of glaucoma based on functional measures can be challenging since it has been shown that retinal ganglion cell loss precedes defects detected on SAP. In addition, SAP is a subjective test prone to inter-test variability making the evaluation of disease progression problematic. Newer algorithms and functional tests are now being used and developed in an attempt to improve the accuracy in the detection of glaucoma and disease progression.

Mutations in IMPG2, Encoding Interphotoreceptor Matrix Proteoglycan 2, Cause Autosomal-Recessive Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results in the absence of seven amino acids in a conserved SEA domain of the IMPG2 protein. Transient transfection of COS-1 cells showed that a construct expressing the wild-type SEA domain is properly targeted to the plasma membrane, whereas the mutant lacking the seven amino acids appears to be retained in the endoplasmic reticulum. Mutation analysis in ten additional index cases that were of Dutch, Israeli, Italian, and Pakistani origin and had homozygous regions encompassing IMPG2 revealed five additional mutations; four nonsense mutations and one missense mutation affecting a highly conserved phenylalanine residue. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The patient with the missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix. Our data therefore show that mutations in a structural component of the interphotoreceptor matrix can cause arRP.

The Relationship between Intraocular Pressure Reduction and Rates of Progressive Visual Field Loss in Eyes with Optic Disc Hemorrhage

To evaluate rates of visual field progression in eyes with optic disc hemorrhages and the effect of intraocular pressure (IOP) reduction on these rates. Observational cohort study. The study included 510 eyes of 348 patients with glaucoma who were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and followed for an average of 8.2 years. Eyes were followed annually with clinical examination, standard automated perimetry visual fields, and optic disc stereophotographs. The presence of optic disc hemorrhages was determined on the basis of masked evaluation of optic disc stereophotographs. Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). The evaluation of the effect of optic disc hemorrhages on rates of visual field progression was performed using random coefficient models. Estimates of rates of change for individual eyes were obtained by best linear unbiased prediction (BLUP). During follow-up, 97 (19%) of the eyes had at least 1 episode of disc hemorrhage. The overall rate of VFI change in eyes with hemorrhages was significantly faster than in eyes without hemorrhages (-0.88%/year vs. -0.38%/year, respectively, P<0.001). The difference in rates of visual field loss pre- and post-hemorrhage was significantly related to the reduction of IOP in the post-hemorrhage period compared with the pre-hemorrhage period (r = -0.61; P<0.001). Each 1 mmHg of IOP reduction was associated with a difference of 0.31%/year in the rate of VFI change. There was a beneficial effect of treatment in slowing rates of progressive visual field loss in eyes with optic disc hemorrhage. Further research should elucidate the reasons why some patients with hemorrhages respond well to IOP reduction and others seem to continue to progress despite a significant reduction in IOP levels. Proprietary or commercial disclosure may be found after the references.

Progressive Visual Field Loss Associated With Optic Disc Drusen Over 25 Years

The authors describe a case with optic nerve head drusen and normal intraocular pressure that was followed up for 25 years. The patient had kinetic perimetry annually until 1997 and static automated perimetry thereafter. From 2002 on, optical coherence tomography scans were also performed but did not permit accurate nerve fiber layer thickness measurement due to peripapillary extension of the optic nerve head drusen. Comparison of visual fields over 25 years reveal a gradual deterioration and demonstrate the value of this diagnostic tool in the study of the disease, especially in cases where nerve fiber layer loss cannot be precisely assessed by optical coherence tomography.

Fundus Autofluorescence and OCT in the Management of Progressive Outer Retinal Necrosis.

A 41-year-old woman with AIDS presented with progressive nasal visual field loss in her right eye. Ophthalmic examination revealed widespread retinal opacification with hemorrhage consistent with progressive outer retinal necrosis, which was confirmed by polymerase chain reaction for varicella zoster virus DNA. The patient was treated with intravenous and intravitreal foscarnet and ganciclovir with improvement clinically. Optical coherence tomography (OCT) and fundus autofluorescence imaging revealed progressive changes indicative of widespread retinal pigment epithelial (RPE) and outer retinal dysfunction. OCT showed progressive changes in macular architecture, including neurosensory elevation, cystoid macular edema, and severe outer retinal necrosis, at initial examination and 1 week and 1 month of follow-up. Fundus autofluorescence revealed stippled hyperfluorescence within extensive zones of hypofluorescence, which progressed during follow-up. OCT and fundus autofluorescence was useful in the characterization of the RPE and retinal anatomy in this patient with progressive outer retinal necrosis.

Target intraocular pressure for stability of visual field loss progression in normal-tension glaucoma

To determine the target intraocular pressure (IOP) level in normal-tension glaucoma (NTG) for visual field (VF) stability following trabeculectomy. Forty eyes of 40 patients who underwent trabeculectomy were enrolled in this study. Progression was determined by a decrease in the Advanced Glaucoma Intervention Study VF defect score of four or more points. The Kaplan-Meier life table method was employed to compare the postoperative VF stability with predetermined IOP levels. The mean postoperative follow-up period was 12 years. At the final visit, the IOP was reduced from 15.2 to 9.4 mmHg on average (P < 0.0001). Reductions in IOP of 20% from baseline were achieved in 70.0% of eyes. The cumulative probability of VF stability was 92.7% in patients having an IOP reduction of >20%, whereas all patients in the poorly controlled IOP group showed progression (P < 0.0001). When IOP values of 9, 10, 11, and 12 mmHg were employed as the cutoff, the best VF prognosis was attained in eyes with a postoperative IOP of 10 mmHg. An IOP reduction of at least 20% from baseline or IOP <or=10 mmHg is recommended as the target postoperative IOP in progressive NTG.

Tight orbit syndrome: a previously unrecognized cause of open‐angle glaucoma

To describe a new syndrome of tight orbit and intractable glaucoma with a poor visual prognosis. A retrospective observational case series of six patients seen at two centres between 2001 and 2007 assessing intraocular pressure (IOP), best-corrected visual acuity and visual field. Three men and three women, ranging in age at diagnosis from 14 to 53 years, demonstrated similar orbital features and progressive visual field loss despite intensive management with medication and laser and operative surgery. Highest IOPs ranged from 30 to 50 mmHg. Trabeculectomy and/or glaucoma drainage devices were attempted in five patients but all failed. One patient underwent orbital decompression with achievement of IOP control. Final IOP at last follow-up was variable; only two patients achieved IOP in the normal range, with the rest ranging from 25 to 40 mmHg. All patients had advanced visual field loss. Tight orbit syndrome presents a serious clinical challenge. Despite maximum medical therapy and surgical intervention IOP is difficult to control, resulting in progressive visual field loss.

Molteno aqueous shunt as a primary surgical intervention for uveitic glaucoma: long‐term results

To evaluate the efficacy of Molteno aqueous shunt as a primary surgical treatment in uveitic glaucoma. Nonrandomized, interventional, retrospective clinical study. The intraocular pressure (IOP), survival rate and complications were analyzed in 30 patients with uveitic glaucoma treated with Molteno implant. The mean follow-up time was 59.3 +/- 18.4 months. Preoperatively, the mean +/- SD IOP was 32.8 +/- 7.5 mmHg (range 20-48), and the mean number of medications was 3.1 +/- 0.6. The mean IOP decreased significantly (p < 0.001) to 17.7 and 15 mmHg at 3 and 6 months postoperatively. The mean number of medications decreased statistically significantly (p < 0.001) from the preoperative number 3.1 to 1.9 three months postoperatively. The number of medications continued to decrease significantly up to 3 years postoperatively. The qualified success rate (Kaplan-Meier estimate) was 97%, 93%, 90% and 85% at 1, 2, 3 and 4 years, respectively. Two patients failed because of hypotony, two patients developed conjunctival erosion and one patient had corneal decompensation. Molteno aqueous shunt as the first glaucoma procedure decreased IOP effectively in uveitic glaucoma. Even after 4 years, the survival estimate was quite high. The IOP decreased continuously during the first year after the surgery, and the medication was slowly tapered even up to 3 years postoperatively. It is suggested that it may be possible to postpone further surgical intervention during the first postoperative year after Molteno implantation even if the IOP is not quite optimal.