American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
January’s American Journal of Ophthalmology:
December’s American Journal of Ophthalmology:
November’s Archives of Ophthalmology:
October’s Archives of Ophthalmology:
Roundup of Other Journals:
Focus On Ophthalmology
A small exploratory study by Ferreri et al. indicates that intralesional rituximab is a well-tolerated treatment approach in marginal-zone and follicular lymphomas of the conjunctiva.
The authors focused on three patient cases, all of whom had relapsed CD20+ conjunctival lymphomas. Two patients had conjunctival mucosa- associated lymphoid tissue (MALT) lymphoma refractory to previous systemic treatment with rituximab. One patient had relapsed follicular lymphoma of the eyelid. Each patient received four weekly intralesional injections followed by six monthly injections of undiluted rituximab together with Xylocaine (lidocaine) 2 percent. The two patients with conjunctival MALT lymphoma experienced complete remission after treatment, indicating that this intraconjunctival approach overcame the primary resistance to this monoclonal antibody. On the other hand, the patient with eyelid follicular lymphoma did not achieve tumor regression after the first injections. However, the addition of autologous serum resulted in lymphoma remission at the end of treatment.
The authors must still define response duration and potential late effects, but they conclude that these findings warrant a large prospective trial.
Soheilian et al. have found that intravitreal injection of clindamycin plus dexamethasone is a viable alternative to the classic treatment of pyrimethamine and sulfadiazine in ocular toxoplasmosis.
In this prospective trial, 34 patients with active ocular toxoplasmosis were randomly assigned to the intravitreal clindamycin plus dexamethasone (IVCD) group and 34 to the classic treatment group. The IVCD group received one to three intravitreal injections of 1 mg clindamycin and 400 µg dexamethasone, while the classic treatment group received six weeks of treatment with pyrimethamine/ sulfadiazine plus prednisolone. The two treatments were equally effective in terms of lesion size reduction.
The authors conclude that while both approaches appear equally effective, the intravitreal injection may offer patients greater convenience, a safer systemic side effect profile, greater availability and fewer follow-up visits. They also warn that these results cannot be generalized to immunocompromised patients, monocular cases and eyes with lesions inside the fovea.
A retrospective case series conducted by Patel et al. has demonstrated that eyelid loading with gold-weight or platinum-chain implantation represents a useful and predictive treatment approach to improving nonparalytic lagophthalmos in patients with dry-eye keratopathy.
Twelve patients with nonparalytic lagophthalmos on blink only (LOB) underwent 21 gold-weight implantation procedures. After a median postoperative follow-up of 15 months, 11 of the 12 patients experienced improvement of LOB and increased frequency of blinking, which resulted in improvement of keratopathy and reduced ocular discomfort. In one case, the gold weight was removed because the patient developed superior corneal thinning and descemetocele. One patient needed ptosis surgery and another developed an allergy to gold and subsequently underwent a platinum-chain exchange.
In addition to the findings that this approach is useful and predictive, the authors stress the importance of looking for blink lagophthalmos in all patients with dry-eye keratopathy as a possible subtle cause of this condition.
Gower et al. tracked fungal keratitis trends in the United States from 2001 to 2007, gathering data from 10 tertiary medical centers.
Overall, 695 fungal keratitis cases were reported during this time period—287 cases involved the use of contact lenses.
The quarterly number of Fusarium keratitis cases among contact lens wearers (CLWs) rose significantly during the time period when ReNu with MoistureLoc was on the market, with the peak number coinciding with the last quarter the product was commercially available. The Fusarium-related fungal keratitis cases among CLWs quickly returned to baseline levels once the product was removed from the market.
However, the number of other filamentous fungal keratitis cases, although small, seemed to increase among refractive CLWs for no apparent reason.
The authors conclude that this latter finding demonstrates the need to create a system to monitor the number of contact lens–related corneal infections.
Sehi et al. examined the impact of surgical IOP reduction on retinal ganglion cell (RGC) function as measured by the pattern electroretinogram optimized for glaucoma screening (PERGLA)—a noninvasive, objective method of measuring RGC function using cutaneous electrodes instead of corneal electrodes.
This cohort study involved 47 eyes of 47 patients with uncontrolled IOP or progressive glaucomatous optic neuropathy who underwent trabeculectomy with antifibrosis therapy (72 percent) or aqueous drainage device implantation (28 percent). The participants underwent PERGLA at two sessions before surgery and at three months following surgery. The authors demonstrated a significant postoperative improvement in PERGLA amplitude consistent with reversal of RGC dysfunction—a finding further supported by the absence of a significant change in PERGLA amplitude in the unoperated fellow eyes with stable IOP.
The investigators call for longitudinal studies to evaluate the possible role of PERGLA as a biomarker for RGC dysfunction in clinical trials involving glaucoma patients.
A study by Campochiaro et al. suggests that anti-VEGF treatment provides long-term benefit in patients with macular edema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).
In this prospective, randomized clinical trial, 20 patients with macular edema due to BRVO and 20 patients with CRVO received injections of anti-VEGF agents. After the third month, the patients were seen every two months and received injections as needed for recurrent edema. At two years, the BRVO patients experienced a mean improvement of 18.8 letters, while the CRVO patients experienced a mean improvement of 8.5 letters. However, frequent injections were required in some of the patients with BRVO and most patients with CRVO. According to the authors, this latter finding suggests that excessive VEGF production represents a long-term problem in many patients with retinal vein occlusion.
They call for additional studies to determine the long-term effects of frequent—possibly monthly—injections and/or the use of higher doses of anti-VEGF agents.
American Journal of Ophthalmology
Leite et al. assessed the agreement of parapapillary retinal nerve fiber layer (RNFL) thickness measurements among three spectral-domain optical coherence tomography (SD-OCT) instruments.
Three hundred and thirty eyes (88 with glaucoma, 206 glaucoma suspects and 36 healthy) from 208 individuals were imaged using RTVue (Optovue), Spectralis (Heidelberg Engineering) and Cirrus (Carl Zeiss) in a single visit. Agreement among RNFL thickness measurements was assessed using Bland-Altman plots. The influence of age, axial length, disc size, race, spherical equivalent and disease severity on the pairwise agreements between different instruments was assessed by regression analysis.
Although RNFL thickness measurements between different instruments were highly correlated, Bland-Altman analyses indicated the presence of fixed and proportional biases for most of the pairwise agreements. In general, RTVue measurements tended to be thicker than Spectralis and Cirrus measurements. The agreement in average RNFL thickness measurements between RTVue and Spectralis was affected by age and spherical equivalent, whereas the agreement between Spectralis and Cirrus was affected by axial length and spherical equivalent. Disease severity influenced the agreement between Spectralis and both RTVue and Cirrus. Disc area and race did not influence the agreement among the devices.
The authors conclude that RNFL thickness measurements obtained by different SD-OCT instruments are not entirely compatible and therefore they should not be used interchangeably. This may be attributable in part to differences in RNFL detection algorithms. Comparisons with histologic measurements could determine which technique is most accurate.
There are various opinions regarding the best prophylaxis against endophthalmitis following cataract surgery. Shimada et al. attempted to prove the hypothesis that during cataract surgery, repeated irrigation of the operative field with povidone-iodine 0.25 percent reduces the anterior-chamber bacterial contamination rate at completion of operation.
In this prospective, interventional case series of 404 consecutive eyes, the operative field was irrigated with infusion fluid in 202 eyes (group A) and with povidone-iodine 0.25 percent in 202 eyes (group B). Bacteriologic culture was performed using the following samples: ocular surface fluid after lid speculum placement and anterior chamber fluid at the completion of surgery. Anterior chamber fluid samples were collected at the beginning and completion of surgery for iodide ion concentration measurement.
Bacterial detection rate in ocular surface fluid was not significantly different between group A and group B, but the rate in anterior chamber fluid was significantly reduced in group B compared with group A. Iodide ion concentrations at the start and end of surgery were 7.5 µg/ml and 3.5 µg/ml, respectively, in group B and less than 0.1 µg/ml both at the start and end of surgery in group A.
In an observational study, Fabian et al. examined the shift in astigmatic error following the use of oral propranolol as first-line treatment for periocular capillary hemangioma.
Three healthy infants (two male) clinically diagnosed with periocular capillary hemangioma underwent cycloplegic refraction measurements at presentation. After a comprehensive clinical evaluation, oral propranolol therapy was started with a loading dose and titrated up to 2 mg/kg per day under monitoring of heart rate, blood pressure and blood glucose alterations. Clinical follow-up and cycloplegic refraction measurements were undertaken at the one-week and two- and three-month visits.
The infants’ mean age at the initiation of propranolol therapy was 6.7 months. A rapid therapeutic effect was noticed in all cases, including a major change in lesion size and color. No complications were recorded during or following treatment. The mean astigmatic error decreased from 2.83 D before propranolol treatment to 1.33 D after one month of treatment. The drug was well tolerated by all three patients, and no side effects were noted.
In a prospective, observational case series, Borrelli et al. evaluated the long-term results of autologous submandibular gland transplantation in eyes with cicatrizing conjunctivitis and determined biomechanical and biochemical features of the resulting salivary tear film.
Fifteen eyes with cicatrizing conjunctivitis and a viable autologous submandibular gland transplantation were compared with 10 eyes with cicatrizing conjunctivitis and a failed submandibular gland transplantation or no submandibular gland transplantation. The authors evaluated BCVA, frequency of tear substitute instillation, severity of dry eye discomfort, lid margin erythema, conjunctival hyperemia, corneal epithelial edema, tear film break-up time, Schirmer test results, and corneal fluorescein and conjunctival rose bengal staining. In a subgroup, they also evaluated central corneal thickness and sensitivity, corneal epithelial barrier function, conjunctival and lid margin flora, and conjunctival impression cytologic analysis. In three patients, preoperative and postoperative tear samples were analyzed for viscosity, surface tension and presence of mucins.
Submandibular gland autotransplantation resulted in long-term improvement of subjective, objective and some ocular surface parameters. Salivary mucins were detectable in salivary tears after submandibular gland transplantation. The viscosity of salivary tears was more similar to normal saliva and the surface tension was intermediate between the two original secretions.
In these patients with severe surface abnormalities and limited options, the authors conclude that submandibular gland autotransplantation may provide long-term relief from pain and reduces the need for frequent installation of lubricants.
In a retrospective, observational case series, Hayes et al. reported 12 cases of postoperative detachment and spontaneous reattachment of Descemet stripping automated endothelial keratoplasty (DSAEK) lenticles.
Patients who had a significant detachment of their DSAEK lenticle during the postoperative period were identified and divided into two groups. Significant detachment was defined as either complete central interface fluid with bare peripheral attachment (group 1) or a free-floating lenticle in the anterior chamber (group 2). Patients who subsequently had a spontaneous reattachment of the lenticle were identified, with data regarding surgical technique and intraoperative and postoperative complications collected for analysis.
The cohort consisted of 12 eyes of 12 patients who met the definition of significant postoperative detachment with subsequent spontaneous reattachment. Four patients had complete central detachment with peripheral attachment (group 1), whereas eight patients had a free-floating lenticle (group 2). Ten of the 12 patients had a successful outcome as defined as an attached and clear DSAEK lenticle. Reattachment was seen as early as five days and as late as seven months after surgery, with reattachment in nine of 12 patients by day 25.
In a prospective, observational, cross-sectional study, Reza et al. evaluated and compared the central corneal thickness measurements of virgin, healthy corneas using a rotating Scheimpflug camera, scanning-slit topography and ultrasound pachymetry.
The authors measured central corneal thickness in 157 healthy eyes of 157 patients without ocular abnormalities other than refractive errors once with a rotating Scheimpflug camera and scanning-slit topography and three times with ultrasound pachymetry. All measurements were performed by a single experienced examiner. The results from scanning-slit topography were given with and without correction for an acoustic correction factor of 0.92.
The average measurements of central corneal thickness by rotating Scheimpflug imaging, scanning-slit pachymetry and ultrasound were 537.15 µm, 542.06 µm and 544.07 µm, respectively. The mean differences between modalities were 6.92 µm between rotating Scheimpflug and ultrasound, 2.01 µm between corrected scanning-slit and ultrasound, and 4.91 µm between corrected scanning-slit and rotating Scheimpflug imaging. According to Bland-Altman analysis, highest agreement was between ultrasonic pachymetry and the rotating Scheimpflug camera.
Archives of Ophthalmology
Wu et al. examined the association of corneal arcus with central corneal thickness (CCT), IOP and the prevalence of primary open-angle glaucoma (POAG) in a population- based cross-sectional study of Malay people living in Singapore.
Participants aged 40 to 80 years underwent systemic and ocular examinations, including corneal curvature, CCT and IOP measurements. Corneal arcus was assessed with a slit-lamp. Corneal arcus was found in 1,747 of 3,015 (57.9 percent) participants.
After adjusting for age, sex and other systemic factors, IOP was higher while CCT was thinner in eyes with corneal arcus. Eyes with corneal arcus had, on average, 1.14 mmHg higher IOP than those without corneal arcus. The prevalence of ocular hypertension, but not POAG, was higher among participants with corneal arcus than among participants without corneal arcus.
The authors conclude that corneal arcus was associated with higher IOP and lower CCT, independent of age, sex and other systemic and ocular factors. These findings may have implications on IOP assessment in persons with corneal arcus.
Hirasawa et al. evaluated the peripapillary distribution of retinal nerve fiber layer (RNFL) thickness in normal Japanese eyes using spectral-domain optical coherence tomography (SD-OCT) and investigated potentially related factors.
The authors measured RNFL in seven concentric peripapillary circles with diameters ranging from 2.2 to 4.0 mm in 259 ophthalmologically normal subjects. The association of RNFL thickness with sex, age, axial length and disc area was analyzed by multiple regression analysis.
Reliable and acceptable OCT images were obtained in 251 of the 259 subjects, and the data of a randomly chosen eye of each subject were analyzed. The average of RNFL thickness decreased linearly from 125 to 89 µm with increase in the measurement diameter. The decay slope of RNFL thickness was smallest in the temporal quadrant, largest in the nasal and inferior quadrants and steeper in eyes with thicker RNFL or smaller optic discs. Age was correlated with RNFL thickness, and the rates of RNFL thinning with age were between –0.30 and –0.18 µm/year in the seven measurement circles. Optic disc area was negatively correlated with RNFL thickness in the inner circles, while positively correlated within the outer circles. Significant correlation was not found between RNFL thickness and sex or axial length after adjusting for the confounding factors.
In a large-scale randomized trial of men, Christen et al. examined whether supplementation with vitamin E or C affects the incidence of age-related cataract.
The authors randomly assigned 11,545 healthy U.S. male physicians aged 50 years or older who were without a diagnosis of cataract to receive 400 IU of vitamin E or placebo on alternate days, or 500 mg of vitamin C or placebo daily. After eight years of treatment and follow-up, the authors confirmed a total of 1,174 incident cataracts responsible for a reduction in visual acuity to 20/30 or worse. For vitamin E, there were 579 cataracts in the treated group and 595 in the placebo group. For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group.
The authors conclude that long-term alternate day use of 400 IU of vitamin E or daily use of 500 mg of vitamin C has no significant beneficial or harmful effect on the risk of cataract.
Onal et al. investigated vision- and health-related quality of life in patients with Behçet uveitis.
Fifty-one consecutive patients with Behçet uveitis were enrolled in the study from Jan. 1 through June 30, 2008. The National Eye Institute Vision Function Questionnaire (NEI-VFQ-25) and the 36-Item Short Form Health Survey (SF-36) were administered before the ophthalmic examination. Sociodemographic and clinical data were also collected.
Patients rated the general health subscale score of the NEI-VFQ-25 and all subscale item scores of the SF-36 lower than the NEI-VFQ-25 subscales related to vision. The NEI-VFQ-25 subscale item scores showed significant differences with respect to age, educational status, uveitis activity and severity, and visual acuity in the better and worse eyes. The SF-36 subscale item scores revealed significant differences according to gender, educational status and the systemic treatment used. In the best model of linear regression, independent variables accounted for 57 percent of the variance in the NEI-VFQ-25 subscale item and for only 23 percent of the variance in the SF-36 subscale item score.
The authors conclude that general health is more affected than that of visual functioning in patients with Behçet uveitis. Sociodemographic and clinical parameters have significant impact on vision and health-related quality of life. Multivariate analysis of the NEI-VFQ-25 and SF-36 subscales reveal that each subscale score is also affected by additional factor(s) other than those analyzed here.
Chauhan et al. reported on the rates of visual field change associated with the previously identified risk factors in the Canadian Glaucoma Study (CGS). They also evaluated the impact of additional IOP reduction on the subsequent rates of visual field change in those patients who reached a CGS endpoint based on total deviation analysis.
Two hundred and sixteen patients with open-angle glaucoma were followed up at four-month intervals with standard automated perimetry and monitored for progression. Patients reaching an endpoint underwent an additional IOP reduction of at least 20 percent. Rates were measured in mean deviation (MD) units per year.
The median MD rate in progressing patients prior to the first endpoint was significantly worse compared with those with no endpoints. An abnormal baseline anticardiolipin antibody level and higher baseline age were associated with faster rates of progression. After the first endpoint, the median IOP was decreased from 18.0 to 14.8 mmHg, resulting in a significant MD rate change from –0.36 to –0.11 dB/year.
The aim of this study by Austeng et al. was to investigate the course of retinopathy of prematurity (ROP) in extremely preterm infants and compare the results with earlier studies of more mature infants.
During the study period of three years, 368 infants developing ROP were followed from the fifth postnatal week until the retina was completely vascularized or until criteria for treatment were met (i.e., type 1 ROP according to the Early Treatment for ROP recommendations).
The study confirms results of previous studies that reported earlier, more frequent and more severe ROP in infants born before 27 weeks of gestation. In addition, new correlations were found regarding time and site of onset of the disease. Postmenstrual age at onset of ROP was related to severity of the disease and nasal onset of ROP was related both to gestational age at birth and to severe ROP.
Roundup of Other Journals
The National Quality Forum defines a “never event” as any intervention involving a wrong site, wrong patient or wrong procedure. Stahel et al. looked at the frequency, root causes and outcomes of wrong-site and wrong-patient procedures utilizing a prospective insurance database of 27,370 physician-reported adverse events that occurred in Colorado from Jan. 1, 2002 to June 1, 2008.
The investigators found a high frequency of surgical “never events,” documenting 25 wrong-patient and 107 wrong-site procedures. These adverse occurrences resulted in significant patient harm in five wrong-patient procedures and 38 wrong-site procedures, with one patient death secondary to a wrong-site procedure.
Analysis of the root cause found a high incidence of diagnostic errors in 56 percent of wrong-patient procedures, including mix-ups in patient medical records, radiographs, laboratory or biopsy samples and tissue specimen samples, and errors in communication.
Wrong-site occurrences were related to errors in judgment and not performing a time-out (which should be done immediately prior to a surgical procedure). The investigators also found that surgical specialties were responsible for significant patient harm in the wrong-patient category but not in the wrong-site group.
In a letter to the editor, Vignal-Clermont et al. warn of the possible visual risks associated with the use of “poppers,” a term for various forms of alkyl nitrate that are used as recreational drugs. While poppers may have a reputation as being innocuous, the authors describe four patients who presented with visual loss resulting from damage to foveal photoreceptors after inhaling the drug.
The first patient reported a reduction in bilateral vision and a central bright dot in both eyes. High-resolution OCT showed damage to the photoreceptor outer segment in the fovea of both eyes. Visual symptoms and clinical features remained the same one month later.
Within three months, three other patients presented with visual loss with central phosphenes after inhaling isopropyl nitrates. Two of these patients experienced a resolution of symptoms over several weeks. The authors hypothesize that the visual symptoms are caused by the release of nitric oxide, a chemical compound that modulates photoreceptor metabolism and function. In addition, because nitric oxide is a potent vasodilator, acute changes in ocular perfusion pressure might contribute to retinal damage.
They conclude that both consumers and ophthalmologists should be cognizant of the possible retinal toxicity associated with poppers.
Chew et al. evaluated the degree of structural loss of retinal nerve fiber layer (RNFL) thickness, macular thickness and macular volume; the degree of functional loss of visual field sensitivity; and the degree of brightness sensitivity and red perception that occur before a relative afferent pupillary defect (RAPD) can be detected in glaucoma patients.
The study involved 50 patients with glaucoma. Twenty-five had RAPD and 25 did not. Optical coherence tomography was used to measure the degree of structural loss of RNFL thickness, macular thickness and macular volume. Automated perimetry measured functional loss of visual field sensitivity.
The authors found that an RAPD could be detected when RNFL thickness decreased to 83 percent of that in the less advanced eye. This decrease equated to a 17 percent loss in RNFL thickness and produced an RAPD in the thinner eye that could be seen using the swinging-flashlight test.
The authors also found that brightness sense differential between the two eyes represented the most accurate surrogate for detecting an RAPD. When the sense of brightness in one eye was less than 64 percent of the other eye, the specificity of this test was 100 percent for an RAPD. However, macular thickness, macular volume and red perception did not necessarily indicate RAPD in glaucoma.
FOCUS ON OPHTHALMOLOGY
Post-hoc analysis of data from the landmark Ocular Hypertension Treatment Study (OHTS) adds to the growing array of appraisals of the monocular trial, which is currently recommended by the Academy’s Preferred Practice Patterns. The analysis strongly implied that a monocular trial is just as effective at assessing a patient’s response to glaucoma medication as a bilateral simultaneous trial, according to Bhorade et al.1 However, the authors note that neither method appears entirely up to the task.
Researchers evaluated responses to medication in 206 patients with ocular hypertension who had been randomized to an observation group in the OHTS and later started on a topical prostaglandin analog (PGA). After a mean baseline IOP was recorded, patients were started on a topical PGA in the eye with higher IOP. They returned in about one month for a second reading. Responses to treatment were recorded in two ways—by the IOP change between baseline and one month in the trial eye alone (unadjusted method) and by using the fellow eye as a control between two visits (adjusted method, known as the monocular trial).
Using Pearson’s correlation, the researchers compared these methods with a “gold standard”—the change between the average of up to three pretreatment IOP measurements and the average of up to three on-treatment measurements. Correlations of IOP change were virtually identical between the “gold standard” and the adjusted and unadjusted methods, indicating that monocular and bilateral simultaneous trials are equivalent for estimating medication response. In addition to these findings, the study showed that, after fellow eyes were started on treatment, the IOP response to a medication in one eye was similar to IOP response to the same medication in the other eye.
VALUE TO CLINICAL PRACTICE: “From this study, we as clinicians need to be reassured that doing a bilateral simultaneous trial is a reasonable way of testing the efficacy of a drug,” said Joel S. Schuman, MD, professor and chairman of ophthalmology at the University of Pittsburgh and director of UPMC Eye Center. “However, it’s better to average a few baseline pressures before a drug is started and average a few pressures after the drug is started.”
“I hope that these results will move clinicians toward obtaining IOP from multiple visits to assess medication response,” said study author Anjali M. Bhorade, MD, assistant professor of ophthalmology and visual sciences at the Washington University School of Medicine in St. Louis. However, this is not always practical. In cases with noncompliant patients or when it is critical to lower IOP immediately, she said, clinicians may need to choose between using the monocular trial or bilateral simultaneous trial.
“Ideally, the one-eyed trial, though, is still worth trying,” said Ivan Goldberg, MBBS, clinical associate professor of ophthalmology and eye health at Sydney University and director of Eye Associates in Sydney, Australia. Not only can the clinician get a “hint of what’s going on,” he said, but the clinician has the opportunity to assess side effects such as allergies and reduce the risk for potentially serious systemic reactions.
“We will really never understand the complete pressure story and its contribution to glaucoma onset and progression, however, until we have real-time continuous pressure measurements,” said Dr. Goldberg.
Given IOP variability, which this study underscores, we must remember not to “hang our hat on this number,” said Dr. Schuman, reminding fellow glaucoma specialists to keep an eye on other changes, as well, such as optic nerve structure and visual field changes.
1 Bhorade, A. M. et al. Ophthalmology 2010;117(11):2047–2054.
Drs. Bhorade, Goldberg and Schuman report no financial interests.