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New Findings from Ophthalmology, AJO, and Archives
American Journal of Ophthalmology:
Roundup of Other Journals:
Welch et al. found that using sodium bicarbonate 8.4 percent to buffer a solution of 2 percent lidocaine with epinephrine resulted in a significant reduction in pain when no adjunctive topical, oral, or intravenous anesthesia or sedation is used.
In this double-blind, prospective, randomized study, 27 male patients and 27 female patients undergoing bilateral, periocular surgery received simultaneous injections, one for each eye, of buffered and unbuffered 2 percent lidocaine with epinephrine. The researchers injected the anesthesia for a 20-second count and a total volume of 1 mL per side. Following the injections, patients rated the pain on each side using a Likert-type visual analogue scale of 0 to 10. Results showed that 65 percent of patients preferred the buffered lidocaine; those who thought the buffered solution was less painful reported a 51 percent reduction in pain level. There were no gender differences in the responses.
The investigators concluded that buffered lidocaine injections should be considered to enhance patient comfort—especially since the cost and time needed to buffer lidocaine injections are minimal.
Incidence of Lens Opacities in Los Angeles Latino Eye Study
According to Richter et al., four-year data from the Los Angeles Latino Eye Study (LALES) indicate that attention to glucose control among diabetics and smoking prevention throughout the community may reduce the risk among Latinos of developing lens opacities. The investigators hope that these findings can help direct public health efforts aimed at reducing cataract risk in Latinos as well as guide future research on the pathophysiology of lens opacities.
The study included 3,471 LALES participants with gradable lenses in the same eye at baseline and at four-year follow-up: 200 participants (5.8 percent) had incident nuclear-only opacities; 141 (4.1 percent) had incident cortical-only opacities; 16 (0.5 percent) had incident posterior subcapsular cataract (PSC)-only opacities; and 88 (2.5 percent) had mixed opacities. Older age, current smoking, and diabetes were independent baseline risk factors for incident nuclear-only opacities, while older age and diabetes at baseline were independent risk factors for incident cortical-only opacities and incident mixed opacities. Female sex was an independent risk factor for PSC-only opacities.
Clinical Features of Ocular Surface Squamous Neoplasms
In a retrospective case series, Kao et al. examined 612 ocular surface squamous neoplasia (OSSN) lesions sent to the Bascom Palmer Eye Institute (BPEI) from 2001 to 2010. They found that several clinical and pathologic factors are associated with higher-grade histologic lesions. These factors include male sex, biopsy at BPEI, temporal and superior locations, lack of corneal involvement, papillomatous and nodular lesions, microscopic multifocality, and positive margins on biopsy.
Over the 10-year study period, 33 percent of the submitted specimens were characterized as mild, moderate, or severe dysplasia; 52 percent were classified as carcinoma in situ; and 11 percent were graded as squamous cell carcinoma. According to the authors, this is the first series to compare associations between pathologic findings and patient and lesion characteristics.
They concluded that their data might help clinicians to more accurately evaluate and anticipate the pathologic grade of conjunctival and corneal lesions that may be OSSN. They also recommended that further research be conducted to study the outcomes and prognosis of OSSN based on these clinical factors.
OCT Detection of RNFL Atrophy in Parkinson Disease
Garcia-Martin et al. tested the reproducibility of retinal nerve fiber layer (RNFL) thickness measurements in patients with Parkinson disease (PD) using Cirrus (Carl Zeiss) and Spectralis (Heidelberg) optical coherence tomography (OCT) systems. The authors also compared the machines’ ability to detect retinal thinning and RNFL atrophy. Although RNFL thickness measurements differed significantly between the machines, the authors concluded that Fourier-domain OCT is a valid and reproducible tool for detecting subclinical RNFL atrophy—especially with the Spectralis Nsite Axonal Analytics protocol.
In this cross-sectional, observational study, 75 patients with PD and 75 age-matched healthy individuals underwent 360-degree circular scans centered on their optic disc using the Cirrus OCT and both the classic glaucoma application and the new Nsite Axonal Analytics software of the Spectralis OCT. The authors compared the differences between healthy eyes and PD eyes using these three applications and evaluated the relationship between thickness measurements provided by each. Repeatability was determined by intraclass correlation coefficients and coefficients of variation.
The authors cautioned that although OCT variability between machines was low, clinicians should carefully evaluate any reduction in RNFL thickness because it may be caused by device variability rather than PD progression. They also noted that the same tomography device should be used to evaluate the RNFL in the detection of disease progression and change.
American Journal of Ophthalmology
Depression Among Patients With Glaucoma
In this cross-sectional study, Wang et al. investigated the prevalence of and risk factors for depression among patients with glaucoma. They found that glaucoma is a significant predictor of depression after adjustment for demographic factors and multiple comorbidities, but not after adjustment for self-reported general health condition. Self-reported measures of vision were significant risk factors for depression in patients with glaucoma, whereas objective measures of vision were not.
This study included 6,760 participants in the National Health and Nutrition Examination Survey over the age of 40 who reported a presence or absence of glaucoma. Demographic and disease-related information was obtained by interview. Self-reported measures of vision were ascertained via items from the Visual Function Questionnaire. Participants underwent visual acuity examination, fundus photography, and visual field testing with screening frequency-doubling technology. The main outcome was presence of depression, which was determined by a score greater than 10 on the Patient Health Questionnaire-9.
Prevalence of depression among participants with and without glaucoma was 10.9 percent and 6.9 percent, respectively. Although the presence of glaucoma was significantly associated with depression after adjustment for demographic factors, this association was not significant after adjustment for self-reported general health condition.
Among participants with glaucoma, objective measures of glaucoma severity were not significant predictors for depression. However, several self-reported measures of visual function were significantly associated with depression.
The authors noted that although this cross-sectional study is useful in assessing disease associations, it cannot establish causation.
Corneal Cross-Linking in Young Patients With Keratoconus
Vinciguerra et al. investigated refractive, topographic, aberrometric, and tomographic outcomes 24 months after corneal cross-linking (CXL) in keratoconus patients younger than 18 years of age. The researchers found that CXL improved uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), most likely by reducing corneal asymmetry as well as corneal and total wavefront aberrations.
In this prospective, interventional case series, 40 eyes underwent riboflavin- and ultraviolet A–induced CXL. The researchers evaluated UCVA, BCVA, sphere and cylinder, topography, aberrometry, tomography, and endothelial cell counts at baseline and at one, three, six, 12, and 24 months. Mean logMAR UCVA and BCVA at baseline were 0.79 and 0.39, respectively. Mean UCVA and BCVA at two years were 0.58 and 0.20, respectively. The improvement in UCVA and BCVA was significant throughout the postoperative follow-up. Mean spherical equivalent refraction showed a significant decrease of 1.57 D at 24 months. Mean simulated keratometry was 46.32 D in the flattest meridian and 51.48 D in the steepest meridian at baseline; at two years, the values were 45.3 D and 50.21 D, respectively. For a 3-mm pupil, there was a significant reduction in whole eye, corneal, higher-order, and astigmatic wavefront aberrations at 24 months.
The authors also observed a significant difference in total coma and total spherical aberration two years after CXL. Mean pupil center pachymetry decreased significantly at six months but recovered by 12 months and remained stable thereafter through the two-year follow-up. Endothelial cell counts did not change significantly.
Corneal Biopsies in the Evaluation of Microbial Keratitis
In a retrospective, observational case series, Younger et al. analyzed the utility of corneal biopsy in the evaluation of infectious keratitis; compared culture and histopathologic exam results of the same specimens; and investigated potential factors related to positive biopsy results. They found that corneal biopsy can be useful for identifying the cause of infectious keratitis in select cases and that culture and histopathologic examination can provide complementary information; however, discordant results may occur. They also discovered that Acanthamoeba and fungal infections are more likely to be identified by histopathologic exam than culture.
The investigators reviewed the medical records of all patients who underwent corneal biopsy due to infectious keratitis at the Jules Stein Eye Institute from June 1989 through June 2009. In general, biopsy specimens were both cultured and examined histopathologically. They analyzed lesion size, lesion progression, and the interval from presentation to biopsy as possible predictors of positive biopsies.
The investigators identified organisms in 20 of 48 (42 percent) consecutive biopsies. Cultures were positive in nine of 47 cases (19 percent), while histopathologic examinations were positive in 19 of 47 cases (40 percent). Culture and histopathologic results were concordant in 30 of 46 biopsies (65 percent) for which both techniques were performed.
Among the 16 discordant cases, only histopathologic examination was positive (i.e., culture negative) in 10 cases: bacteria were seen in four cases, cysts consistent with Acanthamoeba in four cases, and fungi in two cases. Corneal biopsy revealed microorganisms in 12 of 27 patients (44 percent) with negative cultures of corneal scrapings obtained at presentation. None of the potential risk factors were statistically associated with positive biopsies.
Glaucoma in Patients With Autonomic Dysfunction and Abnormal Peripheral Microcirculation
In this prospective, observational study, Park et al. evaluated the visual field (VF) characteristics of normal-tension glaucoma (NTG) patients with either autonomic dysfunction or abnormal peripheral microcirculation. The authors found that NTG patients with low heart rate variability (HRV) or abnormal nailfold capillaroscopy presented with central VF defects. They concluded that vascular risk factors need to be considered in NTG patients who have central VF defects.
The researchers selected patients with clusters of VF defects confined to the central 10 degrees or outside the central 10 degrees (defined as peripheral) in one hemifield. Patients underwent a complete ophthalmic examination and were referred to a rheumatology department, where they underwent HRV assessment and nailfold capillaroscopy. Based on the results, patients were classified into either 1) low, middle, and high HRV groups or 2) normal and abnormal capillaroscopy groups. The central and peripheral VF regions were also further divided into superior and inferior sectors. The authors compared the location and depth of VF defects, as well as the mean deviation and pattern standard deviation of the VFs.
Among patients in both the low HRV and abnormal capillaroscopy groups, VF defects were more frequent and deepest in the superior central sector. The mean deviation was also similar between the two groups; however, the pattern standard deviation was significantly higher in eyes with central defects than in eyes with peripheral defects. The following factors were related to the location of the VF defect: mean deviation, classification by the HRV assessment, and the presence of abnormalities in the capillaroscopy.
Archives of Ophthalmology
Blood Pressure and Changes in Serial Retinal Arteriolar Diameter Measurements
Klein et al. evaluated the relationship between changes in retinal vessel diameters and four outcome measures in the subsequent six-year period: the incidence of diabetic retinopathy (DR), the progression of retinopathy, the incidence of proliferative diabetic retinopathy (PDR), and the incidence of macular edema (ME).
They found that, independent of DR severity level and glycemic control, widening of the retinal venular—but not arteriolar—diameters in people with diabetes was associated with subsequent incidence and progression of DR and incidence of PDR and ME.
They used the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) as the basis for their investigation. The WESDR is a cohort study involving 1,098 persons with either type 1 or 2 diabetes who participated in examinations in three time frames: 1980-1982, 1984-1986, and 1990-1992. The authors graded DR from fundus photographs and used computer-assisted software to measure the retinal arteriolar diameter (as the central retinal arteriolar equivalent) and retinal venular diameter (as the central retinal venular equivalent) at each of the examinations.
They reported that the six-year incidence of DR, progression of DR, incidence of PDR, and incidence of ME from 1984-1986 to 1990-1992 were 56 percent, 39 percent, 15 percent, and 11 percent, respectively. An increase of 10 ?m in the central retinal venular equivalent from 1980-1982 to 1984-1986 was associated with a 26 percent increase in the six-year incidence of DR, a 21 percent increase in the progression of DR, a 19 percent increase in the incidence of PDR, and a 16 percent increase in the incidence of ME. Change in the central retinal arteriolar equivalent was not associated with any of the outcome measures.
Reactivation of Retinopathy of Prematurity After Bevacizumab Injection
In a retrospective case series, Hu et al. described late recurrence and progression of retinopathy of prematurity (ROP) after intravitreal bevacizumab monotherapy. They found that although intravitreal bevacizumab is effective in inducing regression of ROP, the effect might be transient. Reactivation can occur later than with conventional laser therapy and may lead to late retinal detachment.
The authors reviewed the records of nine patients (17 eyes) who experienced reactivation of ROP after initial treatment with bevacizumab. Study data included location and stage of ROP activity, number and timing of treatments, and structural outcomes.
Mean age of the patients whose reactivation required treatment was 49.3 weeks postmenstrual age. The mean interval between initial treatment and reactivation requiring treatment was 14.4 weeks, with a range of four to 35 weeks. Five eyes had progressed to retinal detachment at the time reactivation was detected (four eyes at stage 5 and one eye at stage 4A). Age at retinal detachment ranged from 49 to 69 weeks postmenstrual age. The other 12 eyes received laser for reactivation (four were also treated with additional bevacizumab). None of these eyes progressed to retinal detachment.
Ophthalmology summaries are written by Lori Baker Schena, EdD. American Journal of Ophthalmology summaries are edited by Thomas J. Liesegang, MD. Archives of Ophthalmology summaries are written by the lead authors.
Roundup of Other Journals
No Randomized Trials Found Comparing LASIK With PRK for Hyperopia Correction
Settas et al. set out to determine whether photorefractive keratectomy (PRK) or LASIK leads to safer and more reliable results for the correction of hyperopia. They conducted an extensive literature review, planning to include only randomized, controlled trials comparing PRK with LASIK. However, they could not identify any studies that met these inclusion criteria.
As a result, the investigators could not provide any study results suitable for their analysis. However, they did discuss the results of the five nonrandomized trials they found that compared hyperopic PRK with hyperopic LASIK. The studies generally agreed that LASIK and PRK offered comparable efficacy, safety, and stability to correct hyperopia; but the investigators could not draw any firm conclusions from these data.
The authors suggested that a high-quality, large, well-planned, randomized, controlled trial comparing hyperopic PRK with hyperopic LASIK is necessary to provide more robust and reliable evidence about the two procedures.
Risk of Bleb-Related Infection After Trabeculectomy With Mitomycin C
Rai et al. investigated the cumulative incidence of late-onset bleb-related infection (BRI) following trabeculectomy procedures that are augmented with mitomycin C (MMC). They found that the incidence decreased from 5.7 percent in the mid-1990s, when the technique was first introduced into clinical ophthalmic practice, to 1.2 percent after 1999, when the use of MMC had become relatively common.
The investigators noted that one of the most significant modifications in surgical technique during this period was changing from a limbus-based to a fornix-based conjunctival flap. However, given the retrospective nature of this study, the authors could not definitively assert that a causative relationship exists between these technical changes and BRI.
This study included two cohorts: 194 intraoperative MMC-augmented trabeculectomies performed from 1993 to 1997 and 764 MMC-augmented trabeculectomies performed between 1999 and 2005. The investigators identified 11 cases (5.7 percent) of BRI in the first cohort and nine cases (1.2 percent) of BRI in the second cohort.
Gene Therapy to Treat Wet Age-Related Macular Degeneration
One of the newer approaches to treating wet age-related macular degeneration (AMD) is RetinoStat, which is based on a nonreplicating, nonhuman recombinant lentiviral vector called equine infectious anemia virus. This form of gene therapy is delivered subretinally, where it transduces target retinal pigment epithelial cells and helps produce two proteins, endostatin and angiostatin. Currently, the phase 1 clinical trial of RetinoStat is under way.
Prior to the human trials, Binley et al. conducted this six-month safety and biodistribution study in rhesus macaques and Dutch belted rabbits and found that RetinoStat was well tolerated and safe, with only a mild and transient cellular inflammatory response in the eye. In addition, the level of endostatin and angiostatin proteins in the vitreous peaked about one month after dosing and continued to express during the rest of the study. Findings from this study served to support the launch of the human trials.
Roundup of Other Journals is written by Lori Baker Schena, EdD, and edited by Deepak P. Edward, MD.