Anja Tuulonen

Natural history of normal-tension glaucoma.

OBJECTIVEnA recently reported randomized study described the role of intraocular pressure (IOP) in normal-tension glaucoma (NTG) pathogenesis and the effect of therapeutic lowering of IOP. This is a report of an analysis of the natural course of NTG during the time eyes were not receiving therapy, either in the time interval awaiting randomization or after being randomly assigned not to receive treatment to lower the IOP.nnnDESIGNnAnalysis of prospectively collected data on the long-term course of a cohort of untreated subjects with normal-tension glaucoma, a subset of subjects enrolled in a randomized controlled clinical trial. RANDOMIZATION AND SUBJECT SELECTION: If the field defect in the study eye threatened the point of fixation, the subject was randomly assigned to start on treatment immediately or to be observed without treatment until progression was documented. Otherwise, an eye was randomly assigned only when and if, subsequent to enrollment, it showed visual field progression, progression of optic disc cupping, or a new disc hemorrhage.nnnPARTICIPANTSnData were collected for this report on 160 subjects observed without treatment among a total enrollment of 260. They consist of 49 subjects who were randomly assigned on enrollment not to receive therapy, 24 followed without treatment for a time until later being randomly assigned to treatment, 31 similarly followed without treatment and who were later randomly assigned to be followed for an additional time without treatment, and 56 who enrolled but were never randomly assigned.nnnMAIN OUTCOME MEASURESnVisual field data were used in this report only from the interval during which the eye had not been assigned to receive therapy and were analyzed by two measures of progression: the survival time to meeting a criterion of confirmed localized progression and the rate of change in the mean deviation (MD) index over time.nnnRESULTSnThe four subgroups just described were similar at baseline, except that the average MD index was slightly better for the 56 eyes that never progressed during the period of follow-up. By Kaplan-Meier analysis of all untreated subjects combined, approximately one third showed localized progression within 3 years and about half within 5 to 7 years. Of subjects followed for 3 years or more, 62 of 109 did not show a statistically significant negative slope of MD regressed over time, whereas the others showed a statistically significant MD decline, mainly between -0.2 and -2 db per year.nnnCONCLUSIONSnSome cases of NTG progress more rapidly than others. Although approximately half of cases showed a confirmed localized visual field deterioration by 7 years, the change is typically small and slow, often insufficient to measurably affect the MD index.

Errors in the Diagnosis of Visual Field Progression in Normal-tension Glaucoma

BACKGROUNDnDespite strictly defined criteria for visual field progression in the ongoing Normal-tension Glaucoma Study, the authors noted a surprisingly large number of patients reaching the endpoint. Traditional methods could not be used to check the diagnostic accuracy of their criteria, because no gold standard was established for distinguishing true change from physiologic long-term fluctuation.nnnMETHODSnThe authors developed a statistical method based on the results of duplicate tests for progression in their subjects. This method allowed the authors to assess the sensitivity, specificity, and predictive values of their diagnostic criterion. It also estimated the true incidence of progression and provided standard errors for the estimates.nnnRESULTSnThe authors found that their original strict criteria for progression, based on duplicate testing, produced false calls of progression 57% of the time. By raising the requirement for deterioration and by repeating the entire sequence of duplicate testing once more, the authors have successfully reduced the rate of false calls to 2%.nnnCONCLUSIONnAccuracy in recognizing progression is improved by not accepting small changes as evidence of progression and by confirming the findings on repeat testing.

Intraocular Pressure Reduction in Normal-tension Glaucoma Patients

BACKGROUNDnIn a collaborative study, patients with untreated normal-tension glaucoma were randomly assigned to a marked intraocular pressure reduction group or to a no therapy group. It was anticipated that medical therapy and laser trabeculoplasty would generally not achieve adequate pressure lowering and that fistulizing surgery would be required. This hypothesis was examined using current observations in the study.nnnMETHODSnPatients randomized to the therapy group had a pressure reduction of at least 30% from their last prerandomization level. This was achieved within 6 months by means of fistulizing surgery or with pilocarpine and/or laser trabeculoplasty. Beta-blockers and adrenergic agonists were excluded from both eyes.nnnRESULTSnOf 30 patients with documented stable 30% pressure reduction, 17 (57%) achieved this with topical medication and/or laser trabeculoplasty: 8 with pilocarpine alone, 2 with laser trabeculoplasty alone, and 7 with laser trabeculoplasty after initial topical medication. The remaining 13 (43%) patients required a single fistulizing procedure. There was no statistically significant difference between the mean follow-up time for the nonfistulized group (533.8 +/- 437.6 days) and for the fistulized group (502.7 +/- 344.7 days). Both treatment groups had similar baseline profiles.nnnCONCLUSIONnMarked pressure reduction can be achieved and maintained on a long-term basis by means other than fistulizing surgery in a large proportion of patients with untreated normal-tension glaucoma.

Phacoemulsification with and without trabeculectomy in patients with glaucoma

BACKGROUND AND OBJECTIVEnThis retrospective study was performed to determine the postoperative intraocular pressure (IOP) control in patients with glaucoma who underwent phacoemulsification with and without trabeculectomy.nnnPATIENTS AND METHODSnThirty-five eyes underwent phacoemulsification, and 21 eyes underwent combined surgery. The minimum postoperative follow-up for both groups was 6 months.nnnRESULTSnThe average IOP decreased from 19.7 +/- 4.6 mm Hg preoperatively to 16.3 +/- 3.1 mm Hg in the phacoemulsification group, and from 21.2 +/- 5.9 mm Hg to 14.4 +/- 3.3 mm Hg in the combined group at 6 months (statistically not significant). There was no statistically significant difference between the groups in terms of visual acuity improvement or the number of glaucoma medications.nnnCONCLUSIONnCataract surgery, with phacoemulsification alone and combined with trabeculectomy, induces a statistically and clinically significant reduction of IOP in patients with glaucoma.

Intraocular Pressure-reducing Effect of PhXA41 in Patients with Increased Eye Pressure

PURPOSEnTo establish the dose-response relationship for the effect on intraocular pressure (IOP) and side effects during long-term treatment of patients with ocular hypertension with the prostaglandin F2 alpha (PGF2 alpha) analog PhXA41.nnnMETHODSnA three-center, randomized, double-masked study where IOP, conjunctival hyperemia, and ocular irritation were followed during a 1-month twice-daily treatment with placebo or 35, 60, or 115 micrograms/ml PhXA41 in 60 patients with ocular hypertension, primary open-angle glaucoma, or capsular glaucoma.nnnRESULTSnThe three concentrations of PhXA41 reduced the average IOP between 31% and 38% during the second day of treatment, with only a weak dose-response relationship. The initial effect declined somewhat during the first 2 weeks of treatment but then remained at the same level for the rest of the study, with a pressure reduction of approximately 20% for all three concentrations. On the second day of treatment, mild conjunctival hyperemia could be observed in most treated patients. Nineteen of 45 PhXA41-treated patients, compared with 2 of 15 placebo-treated patients, reported to have mild to moderate ocular irritation. These side effects became less pronounced during the study, and at the end there was little difference in the degree of conjunctival hyperemia between placebo- and drug-treated eyes, and no drug-related ocular irritation was reported with the two lowest concentrations of PhXA41.nnnCONCLUSIONSnIt is confirmed that the PGF2 alpha analog PhXA41 is a major improvement with respect to the effect-side effect relationship and that it may become a valuable new agent for the treatment of glaucoma.

Capsule excision after failed Molteno surgery.

BACKGROUND AND OBJECTIVESnTo determine the frequency of scar tissue formation requiring surgical intervention after single-plate Molteno implantation and the outcome of excision of the encapsulated bleb.nnnPATIENTS AND METHODSnA retrospective study was performed on 95 eyes of 79 consecutive patients who underwent a single-stage Molteno implantation for refractory glaucoma. Fourteen eyes of 12 patients developed an encapsulated bleb. A successful outcome after bleb excision was defined as final intraocular pressure (IOP) between 6 and 22 mm Hg with the same amount of medication as preoperatively or less.nnnRESULTSnAt the end of the mean follow-up of 30 months (range 8 to 75), the mean IOP (19.7 +/- 3.8 mm Hg) after bleb excision was significantly lower than the preoperative IOP (35.2 +/- 10.1 mm Hg; P < .001). The overall conventional success rate was 75%.nnnCONCLUSIONnExcision of the encapsulated Molteno bleb offers an alternative in severely damaged eyes that have undergone several surgical procedures.

Digital imaging and microtexture analysis of the nerve fiber layer.

Purpose: To describe the design of a digital retinal nerve fiber layer (RNFL) imaging techniques and present a new approach to measure the differences in RNFL patterns. Methods: A digital camera body is connected to a wide‐angle camera to obtain images of the RNFL, which are displayed in workstations throughout the clinic. In the on‐line archive, images in Joint Photographics Experts Group (JPEG) format (100 KB per frame) are used. The hypothesis that changes in RNFL structure can be seen as changes in the microtexture of digital images was tested using an information theoretical approach (Kullback Information Distance, KID). A large KID value indicates a large difference, and a small KID value indicates a small difference in microtexture between the two regions. The material of this pilot study consists of 9 patients with glaucoma, 8 patients with ocular hypertension, and 7 normal subjects. Results: The median KID value in the glaucoma group was 3.5, compared with the median KID values of 0.6 in the control groups. Although a trend could be seen in the measured values, because of a small sample size, the differences were not statistically significant. Five of 24 (21%) KID values overlapped between the glaucomatous group and the other two groups. Conclusion: Although digital imaging produces good quality RNFL images, further research is needed to establish minimum accepted specifications for digital imaging. In this pilot study, only the microtexture of the RNFL was measured in digital images. In the future, the approach can be expanded to include also properties of macrotexture and full color palette.

Use of Ocular Hypotensive Medications in Portugal: Pem Study

Purpose: There is scarcity of European data about intraocular pressure (IOP)-lowering prescribing patterns. We aimed to describe and discuss the nationwide prescription of these medications in Portugal. Materials and Methods: This was a cross-sectional study including all patients who were prescribed at least 1 IOP-lowering medication in 2015 in Portugal. All ocular hypotensive drug prescriptions were gathered from the common electronic drug prescription system used by all hospitals and clinics in Portugal. Demographic data, medications prescribed (number and formulation), physician specialty, and costs of medications were provided in an encrypted and anonymous form. Statistical analyses were performed using STATA. Results: A total of 231,634 participants (57% women) were prescribed IOP-lowering medications in 2015, representing 4.0% of the population older than 40 years of age and 2.2% of the Portuguese total population. Mean age was 72±13 years. Topical IOP-lowering therapy accounted for a total of 26 million euros (M&OV0556;) in costs, shared between patients and the national health system. General practitioners (GPs) accounted for 52% of all prescriptions. The most prescribed drugs were latanoprost (28%), timolol/dorzolamide (19%), and brimonidine (14%). Among all, 72% of patients were on monotherapy. Compared with ophthalmologists, GPs presented qualitative differences in their prescription pattern, such as a lower proportion of unit dose prescription. Conclusion: A significant percentage of the Portuguese population is currently treated with IOP-lowering medications, and the majority of them are on monotherapy. Although GPs are responsible for most prescriptions, their prescription pattern is different from that of ophthalmologists. This nationwide study revealed prescription patterns and disclosed the burden of the disease in terms of its medical management.

Letter to the EditorCost-effectiveness

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