Dolders MGT, Nijkamp MD, Nuijts RMMA, Borne B, Hendrikse F, Ament A, Groot W
Br J Ophthalmol 2004;88:1163-8

Modern cataract surgery enables treatment of cataract and (oncoming) presbyopia in cataract patients. An ideal intraocular lens (IOL) would simulate the original function of the crystalline lens and provide the patient with multifocal vision.
Clinical studies have shown improved uncorrectcd near visual acuity and a decreased spectacle dependency for patients with a multifocal IOL compared to patients with monofocal lens implantation. It is hypothesised that this decreased spectacle dependency results in vision related and generic health related quality of life (HROoL) differences between patients with monofocal and multifocal lOLs. Differences in the effectiveness can be related to the possible differences in costs, resulting in a cost effectiveness analysis.

Up to now, there is one cost effectiveness study that compares cataract surgery with implantation of bilateral monofocal and multifocal lOLs. This study reported the cost effectiveness of each treatment using the healthcare payer perspective and divided the average cost per patient by the proportion of patients experiencing a particular vision related outcome, such as costs per spectacle free patient. The specific type of a cost effectiveness analysis (CEA) is a cost utility analysis (CUA) consequences are measured in quality adjusted life years (QALYs). A QALY combines quantity of life (in years) with quality of life (expressed in utilities/preferences) in one measure. A utility is a preference for a certain health state expressed in a cardinal number between 0 (death/worst imaginable health status) and 1 (perfect health/best imaginable health status). The results of a CUA are reported as costs per QALY gained. By using this standard, CUAs in ophthalmology can be compared to CUAs in other healthcare fields. CUAs are particularly useful for decision making about the allocation of scarce resources to maximize social welfare.

The purpose of this study was to analyse the cost effectiveness of foldable monofocal intraocular lenses (lOLs) compared to foldable multifocal lOLs in cataract surgery alongside a prospective, multicentre randomised clinical trial (RCT).

Patients underwent cataract surgery with bilateral monofocal (n = 97) or multifocal (n = 93) IOL implantation. Cost data and patient preferences, using the visual analogue scale (VAS), the time trade-off (TTO), and the standard gamble (SG) technique were obtained preoperatively and postoperatively by structured interviews. The incremental costs (multifocal minus monofocal), mean costs per patient, and differences in preferences were computed.
Mean costs for glasses per patient in the monofocal group were €41.67 and in the multifocal group €149.58. The difference in costs between the multifocal and monofocal group was €-92.09 and was statistically significant (p = 0.008). No significant differences were found in total costs or in effectiveness between the monofocal and multifocal IOL group.

The authors concluded with remarks that the cost effectiveness of multifocal lOLs is reduced to a cost minimisation analysis, because of the inability to demonstrate significant differences in effects. The use of multifocal lOLs in cataract surgery resulted in a significant reduction in costs for patient's postoperative spectacles.

Presumed "Sulfa Allergy" in Patients With Intracranial Hypertension Treated With Acetazolamide or Furosemide: Cross-reactivity, Myth or Reality?

Lee AG, Anderson R, Kardon RH, Wall M
Am J Ophthalmol 2004; 138:114-8

Acetazolamide, a carbonic anhydrase inhibitor, is the mainstay of medical treatment for idiopathic intracranial hypertension. The chemical name tor acetazolamide is N-(5-Sultamoyl-l,3,4-thiadiazol-2-yl)-acetamide. It is a nonbacteriostatic sulfonamide with a chemical structure and pharmacological activity that is different from the sulfonamide antimicrobials. Furosemide is a loop diuretic that is also a sulfonamide medication; it is often used as a second-line or adjunctive agent in patients with intracranial hypertension. Acetazolamide and furosemide, like all medications, may produce mild, moderate, or severe adverse reactions. Previous publications have suggested that patients with a so-called sulfa allergy should not take acetazolamide or furosemide, but there is little compelling clinical or pharmacological evidence to support this recommendation.

The issue is of clinical importance in neuro-ophthalmology because (1) presumed sulfa allergies are common, (2) some allergic reactions may be life threatening, (3) there are no practical tests to determining cross-reactivity among sulfa drugs, and (4) there are few proven alternative medications for the treatment of intracranial hypertension.

The purpose of the study was to determine whether acetazolamide or furosemide produce allergic cross-reactions in patients with self-reported "sulfa allergy." In this retrospective review included patients with intracranial hypertension and a self-reported sulfa allergy treated with either acetazolamide or furosemide seen at the University of Iowa Hospitals and Clinics from 1972 to 2003. All presumed medication-related side effects were collected, including both predictable adverse effects (for example, paresthesias, fatigue) and unpredictable adverse reactions (for example, cutaneous fixed eruptions, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylaxis). Authors reviewed 363 charts. Of these, 329 patients (91%) were excluded. Of the remaining 34 cases that did report a so-called sulfa allergy, 13 (38%) received acetazolamide alone, 7 (21%) received furosemide alone, and 14 (41%) received both acetazolamide and furosemide. Of the 27 patients who received acetazolamide, 10 (37%) had no documented allergic cross-reaction to sulfa, and 2 (7%) cases had urticaria. The remaining 15 (56%) of acetazolamide treated patients experienced predictable adverse reactions for this drug (for example, paresthesias). No patient experienced a severe allergic cross-reaction to sulfa. Of 21 patients who received furosemide, no unpredictable adverse reactions or allergic cross-reactions to sulfa were noted.

The authors found little clinical or pharmacological evidence to suggest that a self-reported sulfa allergy is likely to produce a life threatening cross-reaction with acetazolamide or furosemide. These medications should be considered for intracranial hypertension if the risk to benefit ratio warrants their use.

Classification of Farnsworth-Munsell 100-hue Test Results in the Early Treatment Diabetic Retinopathy Study

Barton FB, Fong DS, Knatterud GL and The ETDRS Research Group
Am J Ophthalmol 2004;138:119-24

Impaired color vision is a common observation among patients with diabetes. In the first Early Treatment Diabetic Retinopathy Study (ETDRS) report on color vision impairment, Farnsworth Munsell 100 (FM 100) test results from patients were compared with test results of normal controls. About 50% of ETDRS patients had abnormal hue discrimination.

Although changes in the total or square root of the FM 100-hue score is one way to describe color vision impairment, the same score may not always correspond to the same impairment. Different patterns of impairment may have the same total error score. The current paper classifies and describes the patterns of color vision impairment present in patients enrolled in the ETDRS. The purpose of this study was to classify and describe clinically meaningful classes of color vision defects using pretreatment Farnsworth Munsell 100-hue results from the Early Treatment Diabetic Retinopathy Study (ETDRS) patients using standard statistical techniques. Farnsworth-Munsell (FM) 100-hue test was successfully administered before initiation of study treatment in each eye of 2701 of the 3711 ETDRS patients. Test results were converted into a Fourier series, classified by cluster analysis in the deferred treatment group of eyes, and verified in the immediate treatment group of eyes as separate samples. Cluster analysis uncovered thirteen distinct patterns. Pattern A (51% or 1366 of the eyes) showed unimpaired hue discrimination and was comprised of younger patients with no or little macular edema. Pattern B eyes (10% or 262) showed generalized impairment of hue discrimination with no main axis defect. Patterns C (Cl, C2, C3), comprising 26% (or 698) of the eyes, showed increasing severity of the yellow-blue diabetic retinopathy defect, associated with increasing mean age and increasing macular edema severity. Patterns D (Dl, D2), comprising 6% (or 164) of the eyes, were similar to the C patterns but showed a stronger yellow-blue defect. Patterns E (El, E2, E3), or approximately 2% (or 38) of the eyes and predominantly male, exhibited the expected pattern for congenital protan defect. Patterns F, G, and H, approximately 6% (or 153) of the eyes, showed distinct patterns of one-sided axes. The nomenclature is arbitrary. The authors concluded with remarks that cluster analysis of FM 100-hue test results has found 13 patterns of impaired hue discrimination, helpful in understanding color vision defects in diabetes mellitus.

Functional Visual Outcomes of Cataract Extraction in Monocular Versus Binocular Patients

Pomberg ML, Miller KM
Am J Ophthalmol 2004; 138:125-32

Functionally monocular cataract patients not uncommon in ophthalmic practice, yet many ophthalmologists are reluctant to recommend or perform cataract surgery for these patients at the same level of visual acuity disability as their binocularly sighted patients. A reluctance to operate is understandable given the consequences of a poor surgical outcome, but it is highly likely that monocular patients suffer a greater functional impairment than binocularly sighted counterparts with the same level of visual acuity disability, because the acuity loss that monocular patients experience is in their better seeing eye.

The purpose of this study was to determine the change in functional vision that occurs with cataract surgery in a group of monocular patients compared with a group of binocularly sighted control subjects. In this retrospective case control study subjects comprised 100 functionally monocular patients who underwent cataract surgery at the Jules Stein Eye Institute between 1996 and 2002. Control subjects were 100 binocularly sighted patients, matched to study subjects by age, sex, and timing of surgery. A single ophthalmologist performed all of the operations using an ultrasonic phacoemulsincation technique. Best-corrected visual acuity (BCVA) was measured before and after surgery using a conventional visual acuity monitor. Self-reported visual function was assessed before and after surgery using the Visual Function 14 (VF-14) questionnaire. Paired t tests were used to report statistical significance. The monocular group had significantly worse mean BCVA than the binocular group before and after surgery, but the improvement experienced by the two groups was statistically indistinguishable (P = .913). Mean global VF-14 score was significantly worse for the monocular than the binocular group before and after surgery, but the monocular group experienced a significantly greater improvement (P = .00164) in VF-14 following surgery (20.4 points for the monocular group vs 10.1 points for the binocular group). Monocular patients report twice as much improvement in functional vision as binocular patients despite similar BCVA gains. This may be because monocular patients had cataract surgery on their better seeing eye, whereas binocular patients typically had surgery on their poorer seeing eye.

Optical Coherence Tomography (OCT) Macular and Peripapillary Retinal Nerve Fiber Layer Measurements and Automated Visual Fields

Wollstein G, Schuman JS, Price LL, Aydin A, Beaton SA, Stark PC, Fujimoto JG and Ishikawa H
Am J Ophthalmol 2004; 138:218-25.

Glaucoma is characterized by a gradual loss of retinal ganglion cells (RGCs) and thinning of the nerve fiber layer (NFL). While the etiology of this damage is uncertain, the loss itself is well documented. Currently, RGC loss is assessed clinically using biomicroscopic examination as NFL loss or less directly as optic nerve head cupping. The functional effect of RGC loss is evaluated clinically using perimetry. Substantial RGC loss has been shown to occur in the macula in primate experimental glaucoma. Garway-Henth and associates demonstrated that because of the redundancy of ganglion cells in the macula, greater loss of ganglion cells is required in the central compared with peripheral visual field (VF) for equal effects on visual sensitivity. Additionally, since ganglion cell bodies have 10 to 20 times the diameter of their axons, it has been suggested that macular imaging might enhance initial detection of glaucomatous damage. Optical coherence tomography (OCT) is the optical equivalent of ultrasonography with high in vivo resolution.

The purpose of this study was to investigate the structure-function relationship between optical coherence tomography (OCT) macular retinal and peripapillary nerve fiber layer (NFL) thickness and automated visual field (VF) findings. In this retrospective institutional study, consecutive eyes (101 subjects) from a glaucoma service were included. All the participants had full ophthalmic evaluation, VF testing and prototype OCT scanning at the same visit. Orthogonal OCT macular analysis was obtained to maximize the sampling of the area of interest. Pearson age adjusted correlation was determined between macular retinal thickness and peripapillary NFL thickness. Area under the receiver operator characteristics (AROC) curves for the association between macular retinal thickness and peripapillary NFL thickness and VF findings were calculated in a subgroup of eyes without VF defect and eyes with VF defect confined to one hemifield. The correlation between macular retinal and peripapillary NFL measurements ranged between r = .27 to .54 for quadrants, .44 to .55 for hemiretina, and .52 for the overall mean. Areas under the receiver operator characteristics for macular thickness were higher in areas corresponding to the VF defect location than the non-corresponding locations. Areas under the receiver operator characteristics for peripapillary NFL thickness were higher than for the macular retinal thickness. Including both macular retinal thickness and peripapillary NFL thickness measurements in the logistic regression model yielded AROCs (range: .69-.77) similar to those found for the peripapillary NFL alone.

The authors concluded that macular retinal thickness as measured by OCT, was capable of detecting glaucomatous damage and corresponded with peripapillary NFL thickness; however, peripapillary NFL thickness had higher sensitivity and specificity for the detection of VF abnormalities. Optical coherence tomography (OCT) is the optical equivalent of ultrasonography with high in vivo resolution.

1. Garway-Heath DF, Caprioli J, Fitzke FW, et al. Scaling the hill of vision: the physiological relationship between light sensitivity and ganglion cell numbers. Invest Ophthalmol Vis Sci 2000; 41:1774-82.

Therapeutic application of tissue plasminogen activator for fibrin reaction after cataract surgery

Özveren F, Eltutar K
J Cataract Refract Surg 2004; 30:1727-31

The risk for fibrin reaction after uneventful large-incision extracapsular cataract extraction (ECCE) is between 6% and 8%. The risk decreases to 4% with small incision cataract surgery but is related to the duration of the operation. If surgery exceeds 50 minutes, fibrin reaction occurs in up to 22.4% of normal eyes. In patients with concomitant disease such as diabetes, pseudoexfoliation, uveitis, and glaucoma, the prevalence increases to 54%. Postoperative fibrin reaction decreases the success of surgery by lowering postoperative vision. The course of treatment with conventional methods, such as longterm use of steroids and mydriatics, can lead to many complications. If treatment fails, the fibrin reaction organizes and forms an interpupillary fibrin membrane that dislocates the intraocular lens (IOL) or causes pupillary block glaucoma.

Several studies have used 10 to 25 ug of recombinant tissue plasminogen activator (rtPA) to treat fibrin reaction; however, complications occurred, even at these low doses. The purpose of this study was to evaluate the efficacy and safety of therapeutic application of recombinant tissue plasminogen activator (rtPA) for fibrin reaction after uneventful cataract surgery. In a prospective study between January and June 2000, 26 eyes of 26 patients with fibrin reaction after uneventful cataract surgery received 3 ug of intracameral rtPA. Patients were evaluated for recurrences of fibrin reaction or complications by slitlamp biomicroscopy 2, 12, and 24 hours, 1 week, and 1 and 6 months after rtPA application. Intraocular pressure (IOP) was measured by Gold mann applanation tonometry. Visual acuity was tested using a standard Snellen chart 1 week after rtPA application.
All 26 eyes had complete fibrinolysis. Three eyes (11.5%) had corneal edema that lasted fewer than 24 hours. Visual acuity improved by 0 to 7 lines in 19 patients (73.1%). No patient had an increase in IOP. At 6 months, no patient had hyphema or recurrence of fibrin reaction.
The authors concluded with remarks that complete-lysis of fibrin after cataract surgery with conventional topical medications can take a long time and is not successful in some patients. Intracameral application of 3 ug rtPA was an efficient, safe method for the treatment of fibrin reaction after cataract surgery.

Light-transmission-spectrum comparison of foldable intraocular lenses

Ernest PH
J Cataract Refract Surg 2004; 30:1755-8

The human eye is exposed to ultraviolet (UV) light between approximately 286 nm and 400 nm. From this exposure, only light between 300 nm and 400 nm reaches the inside of the eye because of the absorption properties of the cornea. The retinal exposure to this range of UV light is minimal as a result of additional light attenuation by the crystalline lens. Before the advent of UV blocking lOLs, cataract surgery resulted not only in the removal of the cataractous lens but also in the removal of the protection the crystalline lens normally affords the retina. During the early 1980s, the use of UV-light attenuating lOLs became widespread. Manufacturers of lOLs recognized that the normal adult human lens was an effective UV absorber and that to effectively replace this lost function, an IOL would have to absorb UV light. All lOLs manufactured today that I am aware of contain a UV chromophore that effectively protects the retina from exposure to light up to 400 nm.

In addition to providing protection from UV light exposure, the natural human lens decreases retinal exposure to blue light in the 400 to 500 nm range. The logic of replacing the natural human crystalline lens with an IOL that mimics its UV absorption properties could be extended to the replacement of the crystalline lens by an IOL capable of attenuating blue light. The purpose of this study was to compare the light transmittance of 4 currently marketed intraocular lenses (lOLs) with that of the new AcrySof® Natural IOL (Alcon Laboratories, Inc.), which is designed to mimic the light-attenuating characteristics of the human crystalline lens. Light-transmission spectra of 4 commonly implanted lOLs were compared with the spectrum of the AcrySof Natural IOL (model SN60AT).

While the 4 other foldable lOLs transmitted nearly 100% (near 0% absorption) of the light in the 400 to 500 nm (blue-light) region, the AcrySof Natural IOL absorbed a significant portion of blue light. Comparison of the spectrum of the AcrySof Natural IOL with the spectrum of human crystalline lenses of various ages showed that the AcrySof Natural lens closely mimics the light-attenuating characteristics of the human crystalline lens. The authors concluded with remarks that the AcrySof Natural IOL provides a transmission spectrum more like that of a human crystalline lens than do other commonly implanted foldable lOLs. The Natural IOL reduces ultraviolet and blue-light exposure to the retina, mimicking the filtering normally provided by the human crystalline lens.