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September 2007

Journal Highlights
New Findings from Ophthalmology, AJO and Archives

September's Ophthalmology:

August's Ophthalmology:

September's American Journal of Ophthalmology:

August's American Journal of Ophthalmology:

July's Archives of Ophthalmology:

June's Archives of Ophthalmology:

Roundup of Other Journals:


Antibiotic Comparison for Bacterial Keratitis
September’s Ophthalmology

In a prospective trial, Constantinou et al. randomized 78 patients with bacterial keratitis to a fortified tobramycin/cephazolin group, 77 patients to a moxifloxacin group and 74 patients to an ofloxacin group.

Patients received the assigned medication every hour for 48 hours, and on the third day were switched to every hour by day and every two hours at night. The medication continued to be tapered over the following week. The researchers found that all three antibiotic treatments were equally effective, with resolution of keratitis and healing of the ulcer occurring in 94 percent of patients. The safety profiles were also similar, with all three medications appearing to be safe and well-tolerated.

Incipient Nonarteritic Anterior Ischemic Optic Neuropathy
September’s Ophthalmology

In a study involving 60 eyes of 43 patients seen from 1973 to 2000, Hayreh and Zimmerman argue that incipient nonarteritic anterior ischemic optic neuropathy (NAION) is a distinct clinical entity.

While classic NAION presents with a history of sudden visual loss, segmental optic disc edema initially and optic disc-related visual field defects, in incipient NAION there is optic disc edema with a segmental pattern similar to that seen in early classic NAION and no visual loss attributable to classic NAION. The authors note that incipient NAION may represent an early stage in the NAION process, an assertion supported by the fact that of the 60 eyes with incipient NAION, more than half had classic NAION simultaneously or at another time in the fellow eye. In addition, 25 percent of the eyes with incipient NAION progressed to classic NAION. They urge clinicians to consider incipient NAION in patients who have had classic NAION in the fellow eye, in diabetics and in those at high-risk for NAION.

Periocular Corticosteroid Injection in Subfoveal Choroidal Neovascularization
September’s Ophthalmology

A study by the Neovascular Age-Related Macular Degeneration, Periocular Corticosteroids and Photodynamic Therapy Trial Research Group has found no advantage in giving patients with subfoveal choroidal neovascularization secondary to AMD a single periocular corticosteroid injection as adjunctive therapy to photodynamic therapy.

In this randomized, two-center clinical trial, 67 participants received either PDT alone or a single periocular triamcinolone injection administered via the posterior superior sub-Tenon’s route prior to PDT. They were examined one, three and six months after treatment. At three months, 94 percent of the corticosteroid group and 90 percent of the no-corticosteroid group experienced fluorescein leakage, while mean visual acuity was 20/100 for the corticosteroid group and 20/125 for the no-corticosteroid group, decreasing an average of 1.5 and 0.9 lines from baseline, respectively.

Misdiagnosis of Hydrophilic Acrylic IOL Opacification
September’s Ophthalmology

In a retrospective, interventional case series, Haymore et al. describe eight patients with MemoryLens (Ciba Vision) hydrophilic acrylic IOLs who were misdiagnosed as having a vitreous condition or posterior capsular opacification prior to being correctly diagnosed with IOL opacification.

All eight patients underwent IOL implantation between August 1999 and March 2000 and presented with complaints of decreased visual function 13 to 58 months later.

Four of the patients initially diagnosed with PCO underwent Nd:YAG laser capsulotomy. The remaining four were diagnosed with some form of vitreous involvement and underwent vitrectomies. Six of the eight patients underwent subsequent IOL exchange, with three subsequently experiencing endophthalmitis, cystoid macular edema and retinal detachment. Scanning electron microscopy confirmed calcified deposits on the surface of two explants.

Practice Patterns Compared With Claims Data in Treatment of Glaucoma
September’s Ophthalmology

Quigley et al. measured the validity of large claims databases in two areas: estimating patient cooperation with eye drop therapy and assessing physician adherence with guidelines from a preferred practice pattern (PPP).

The researchers abstracted data from 300 charts of individuals prescribed a prostaglandin eye drop for primary open-angle glaucoma (OAG). They assessed degree of agreement between chart notations by physicians and the claims database, and compared physician behavior to a PPP for OAG using a new metric. While chart data confirmed that the claims database accurately identified the specific glaucoma eye drop prescribed, physicians often identified long-term OAG patients as new to treatment. In addition, they varied in adherence to the PPP, performing visual field tests and optic disc imaging in many patients, but frequently failing to set target IOP and assess the angle by gonioscopy.

Early Treatment for Idiopathic Retinitis, Vasculitis, Aneurysms and Neuroretinitis
August’s Ophthalmology

A review of the largest cohort of patients with idiopathic retinitis, vasculitis, aneurysms and neuro-retinitis (IRVAN) by Samuel et al. indicates that early panretinal laser photocoagulation should be considered when angiographic evidence of widespread retinal nonperfusion is evident, and prior to, or shortly after, neovascularization has developed.

They also propose a functional staging system to optimize treatment. They conducted a review of 10 patients originally reported in 1995, and then followed up on seven of them while adding 12 additional patients.

The investigators found that all of the eyes treated in the second stage of their staging system maintained 20/20 vision, and none of these eyes progressed to a more advanced stage of the disease. Eyes treated in later stages lost visual acuity, and some progressed to neovascularization or neovascular glaucoma despite aggressive treatment with panretinal laser photocoagulation and vitrectomy.

The authors conclude that the visual prognosis in IRVAN may depend on early treatment for ischemic retinal disease.

Factors Associated With Recurrence of Amblyopia After Patching
August’s Ophthalmology

Holmes et al. looked for factors associated with recurrence or regression of amblyopia in a group of 69 children. A previous study involving this cohort had found that children between ages 3 and 8 who were successfully treated with six to eight hours of daily patching for amblyopia secondary to anisometropia, strabismus or both had fourfold greater odds of recurrence if patching stopped abruptly rather than when it was reduced to two hours per day prior to cessation.

In the current study, the authors found that recurrence of amblyopia was associated with better visual acuity at the time patching stopped, the improvement of a greater number of lines during the previous treatment, and a prior history of recurrence. In addition, orthotropia or excellent stereoacuity at the time of patching cessation did not appear to offer a protective effect.

The authors recommend long-term monitoring of these children following completion of amblyopia treatment to detect and treat any recurrence of the condition.

Delayed Removal of Intraocular Foreign Bodies in Soldiers
August’s Ophthalmology

A study by Colyer et al. of troops deployed in the war in Iraq from February 2003 to November 2005 demonstrates that there is no significant advantage of early removal of intraocular foreign bodies (IOFBs), either with regard to postoperative visual acuity or endophthalmitis rates, as long as primary closure is done within hours of injury and broad-spectrum antibiotics are started.

The researchers studied 79 eyes of 70 patients with an average IOFB size of 3.7 mm and median time to IOFB removal of 21 days. They found that poor visual outcome and postoperative complication rates were related to extensive intraocular injury.

They conclude that delayed IOFB removal with a combination of systemic and topical fluoroquinolone agents—primarily gatifloxacin, moxifloxacin or levofloxacin—can result in good visual outcomes without an increased risk of adverse effects.

Intravitreal Bevacizumab for Uveitic Macular Edema
August’s Ophthalmology

A retrospective, interventional case series of 13 patients by Coma et al. undergoing treatment for recalcitrant uveitic macular edema indicates that a single intravitreal injection of bevacizumab is well-tolerated, and is associated with short-term improvement of visual acuity and decreased optical coherence tomography thickness.

The authors reviewed the charts of patients who received one 2.5-mg intravitreal injection of bevacizumab in one eye. Eighty-four days or more after this injection, six patients had a decrease in foveal thickness and five patients demonstrated an improvement in visual acuity by 2 lines or more. In addition, none of the patients experienced significant ocular or systemic adverse effects.

The authors, while emphasizing the importance of uveitic remission for patients undergoing therapy for persistent cystoid macular edema, conclude that their findings warrant a randomized clinical trial further exploring the use of intravitreal injection of bevacizumab. They postulate that repeated therapy will likely be required since CME will probably return over time.

Flaps Created by Femtosecond Laser Compared to Microkeratome
August’s Ophthalmology

A study by Patel et al. shows a lack of clinically significant differences in vision during the first six months following LASIK between flaps created by a bladeless femtosecond laser or by a mechanical microkeratome.

In this randomized, controlled study, one eye in each of 21 patients was randomized to flap creation with a femtosecond laser with an intended thickness of 120 µm and the fellow eye to flap creation with a mechanical microkeratome with an intended thickness of 180 µm.

The researchers found that corneal backscatter was 6 percent higher after the bladeless LASIK compared to the microkeratome at one month, but not at three or six months. In addition, high-contrast visual acuity, contrast sensitivity and forward light scatter did not differ between treatments at any point during the follow-up period. Finally, at three months, five patients preferred the bladeless eye, seven patients preferred the microkeratome eye and nine patients had no preference.

American Journal of Ophthalmology

Crystalens vs. ReZoom vs. ReStor IOL Implants
September’s AJO

Pepose et al. compared the visual performance of patients with bilateral vs. combination Crystalens, ReZoom and ReStor IOL implants in a prospective, nonrandomized study.

Forty-nine patients were implanted with bilateral Crystalens, ReStor or ReZoom IOLs; combined Crystalens and ReStor IOLs; or combined Crystalens and ReZoom IOLs after phacoemulsification cataract surgery. Monocular and binocular testing four to six months after surgery included UCVA and BCVA at distance, intermediate and near vision; mesopic contrast sensitivity function with and without glare; and quality-of-life and vision surveys six months after surgery.

Monocular testing showed that eyes with the Crystalens accommodating IOL had statistically better best-corrected distance, uncorrected and distance-corrected intermediate, and best-corrected near vision. Eyes with the ReStor multifocal IOL had better uncorrected near vision and required the lowest reading add but had the worst uncorrected and distance-corrected intermediate vision. Monocular mesopic contrast sensitivity with and without glare was better with the Crystalens IOL vs. either multifocal IOL at specific spatial frequencies. The binocular subjective quality-of-vision and quality-of-life questionnaires were favorable for the bilateral Crystalens group.

The authors conclude that any combination of Crystalens in one or both eyes was better for intermediate vision. Any combination of ReStor in one or both eyes was better for near vision. The Crystalens and ReStor combination had better mean intermediate and near vision overall. A multifocal IOL in one or both eyes was associated with lower contrast sensitivity and more subjective reports of photic phenomena. The accommodating and multifocal IOL combinations elicited fewer night glare symptoms than either bilateral multifocal IOL, but more than with bilateral Crystalens implantation.

Posterior Vitreous Detachment and the Incidence of Delayed Retinal Breaks
September’s AJO

Coffee et al. studied the necessity for an early follow-up examination after an initial funduscopic examination with negative results for retinal tears in patients with acute, symptomatic posterior vitreous detachment (PVD).

This retrospective, case-control study reviewed the records of patients seeking treatment over a 4.5-year period who were diagnosed with an acute, symptomatic PVD. A Medline search was also performed to identify all published observational case studies reporting vitreoretinal pathologic features after acute, symptomatic PVD.

The incidence of retinal tears in eyes with a symptomatic PVD was 8.2 percent. The overall rate of retinal breaks in the meta-analysis portion of the study was 21.7 percent. In total, 1.8 percent of patients had retinal tears that were not seen on initial examination. Of the 29 patients with delayed-onset retinal breaks, 24 (82.8 percent) had at least one of the following: vitreous hemorrhage at initial examination, hemorrhage in the peripheral retina at initial examination or new symptoms.

The authors conclude that if an initial examination of a patient with an acute, symptomatic PVD is negative for retinal tears, the necessity of early follow-up may be best determined by the presence of pigmented cells in the vitreous, vitreous hemorrhage or retinal hemorrhage. Most patients with symptomatic PVD may not need an early follow-up examination.

Stray Light Effects With Aging and Lens Extraction
September’s AJO

Van den Berg et al. assessed possible gains and losses in stray light values among patients with and without cataracts.

The study had a cross-sectional design with data derived from a multicenter study on visual function in automobile drivers. In both eyes of 2,422 subjects, visual acuity, stray light on the retina and lens opacity were determined. Three groups were defined: 220 pseudophakic eyes, 3,182 noncataractous eyes and 134 cataractous eyes.

Noncataractous stray light values increased strongly with age, doubling by the age of 65 years, and tripling by the age of 77 years. The cataractous eyes had relatively mild stray light increase. In pseudophakia, stray light values were very low, better even than in the noncataract group. Visual acuity and stray light were found to vary quite independently.

The authors conclude that lens extraction may not only improve the condition of the cataractous eye, but also may improve the age-normal eye. Lens extraction potentially reverses the strong age increase in stray light value, independently from visual acuity.

Pars Plana Vitrectomy for Retained Lens Material After Cataract Surgery
September’s AJO

Merani et al. evaluated the management and outcomes of patients undergoing pars plana vitrectomy for retained lens material after cataract surgery. They also examined the risk factors for poor visual outcome, retinal detachment, raised IOP and cystoid macular edema.

This was a retrospective, consecutive case series of 223 eyes of 223 patients with a mean follow-up of 20.5 months after vitrectomy. A standard three-port pars plana vitrectomy/lensectomy was performed. Final BCVA was 6/12 or better in 159 (71 percent) patients. Retinal detachment occurred in 20 (9 percent) patients, with 11 diagnosed before or during vitrectomy and nine occurring after vitrectomy. Ten (5 percent) patients developed raised IOP, and 42 (23 percent) developed cystoid macular edema. Poor final visual acuity was associated with retinal detachment and with poor visual acuity at presentation. There was a significant association between retinal detachment and a long interval (i.e., greater than 30 days) between cataract surgery and vitrectomy, and between retinal detachment and younger age.

Visual acuity results in this study compared favorably with previously published reports. Although the overall rate of retinal detachment was low, it was significantly higher in those with a delayed interval between cataract surgery and vitrectomy, and was significantly associated with a poorer visual outcome. The authors therefore suggest early vitreoretinal surgery.

Vitreous Presentation During Cataract Surgery
August’s AJO

Vitreous presentation during cataract surgery poses a risk for final visual acuity. In this study, Gaster and Collins compared BCVA at two, three and four years following implantation of anterior chamber (AC) IOLs and posterior chamber (PC) IOLs after vitreous presentation during extracapsular cataract extraction in patients having sufficient capsular support for a nonsutured PCIOL.

In this prospective, long-term clinical trial, patients at 19 Veterans Affairs Medical Centers were randomized to receive either a PCIOL (230 patients) or an ACIOL (208 patients). Patients having insufficient capsular support (143 patients) and a random sample of nonvitreous presentation patients (521 patients) were prospectively followed in the same fashion.

There was no significant difference on the major outcome measure of BCVA of 20/40 or better between the PCIOL and ACIOL groups at two (88.7 percent vs. 82.2 percent), three (82.5 percent vs. 91.8 percent) and four (88.6 percent vs. 92.6 percent) years of follow-up. The patients with insufficient capsular support had significantly worse BCVA than the other three groups at two and four years.

Although prior studies indicated that the visual result of a PCIOL was better than the ACIOL at one year, it was not maintained in later years. The poor results for patients with insufficient capsular support reported previously at one year in other reports continued at two and four years.

Ocular Dominance and Its Influence in Monovision
August’s AJO

Leal et al. analyzed the response of normal emmetropic subjects to different ocular dominance tests and analyzed the influence of this response in surgically induced monovision.

In a prospective study of diagnostic accuracy, nine different tests were carried out in a group of 51 emmetropic subjects to determine both motor and sensory ocular dominance. For analysis, patients were divided into two groups according to age. All patients had a normal ophthalmologic examination, including normal binocular vision and good stereoacuity.

There was a significant degree of uncertainty or ambiguousness to the results except in the hole-in-card and kaleidoscope tests, which were more reliable. When the tests were compared, two by two, the correlation or equivalence found was low and was much lower if tests were compared three by three.

The study concluded that most individuals do not demonstrate clear ocular dominance. Instead, there may be a constant alternating balance between both eyes in most emmetropic persons, but not in those with pathologic features. It seems appropriate to evaluate a patient’s dominance before monovision surgery to identify those individuals with clear dominance.

Long-Term Results of Thin Corneas After Refractive Laser Surgery
August’s AJO

Kymionis et al. reported the long-term refractive results of photorefractive keratectomy (PRK) and LASIK in patients with thin corneas.

This retrospective, nonrandomized, follow-up study included 63 patients (124 eyes) who had a preoperative central corneal thickness of less than 500 µm and had completed at least one year of follow-up examinations after surgery. Thirty-five patients (68 eyes) underwent PRK and 28 patients (56 eyes) underwent LASIK.

The mean preoperative corneal pachymetry was 484 µm and 482 µm for LASIK and PRK, respectively. No intraoperative complications were reported, and none of the included eyes developed postrefractive corneal ectasia. The mean predictability for the PRK group was 0.08 D with a standard deviation of 0.40 D, and the mean predictability for the LASIK group was 0.14 D with a standard deviation of 0.55 D.

The authors conclude that refractive laser surgery with LASIK or PRK in patients with thin corneas seems to be a reasonably safe and predictable technique for myopic refractive corrections.

Reopening of Previously Closed Macular Holes After Cataract Extraction
August’s AJO

In a retrospective, comparative, consecutive case series, Bhatnagar et al. evaluated the frequency with which macular holes reopen after cataract extraction.

Two hundred eleven eyes with idiopathic macular holes closed by vitrectomy were divided into four groups: group 1 (56 eyes that underwent prior cataract extraction), group 2 (86 eyes that underwent vitrectomy then cataract extraction), group 3 (41 eyes that underwent vitrectomy only), and group 4 (28 eyes that underwent vitrectomy and cataract extraction as a combined procedure). The main outcome measure of macular hole reopening was evaluated in relationship to multiple variables.

Twenty-four macular holes reopened (11 percent), with the most in group 2, (17; 20 percent). Cox multivariate analysis failed to demonstrate an association between duration of hole, serum use, internal limiting membrane peeling or stage and reopening of a macular hole. Cox analysis showed a fourfold increased risk of reopening in group 2 eyes. Eyes with cystoid macular edema after cataract extraction had a sevenfold increased risk of macular hole reopening. Kaplan-Meier analysis showed increased rates of macular hole reopening in group 2 eyes compared with the other three groups combined.

The authors conclude that cataract extraction after successful vitrectomy for macular hole, when complicated by cystoid macular edema, seems to increase the risk of macular hole reopening.

More Online

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Archives of Ophthalmology

Agreement of Plus Disease Diagnosis in Retinopathy of Prematurity
July’s Archives

Chiang et al. measured agreement of plus disease diagnosis among retinopathy of prematurity experts.

A set of 34 wide-angle retinal photographs from infants with ROP were compiled and interpreted independently by 22 experts. Eligible ROP experts were defined as practicing pediatric ophthalmologists or retina specialists who met at least one of three criteria: having been a study center principal investigator for either the Cryotherapy for ROP or Early Treatment for ROP studies, having been a certified investigator for either study or having coauthored more than four peer-reviewed ROP manuscripts. Diagnostic agreement was analyzed by using three-level (plus, pre-plus or neither) and two-level (plus or not plus) categorizations.

In the three-level categorization, all experts agreed on the same diagnosis in four (11.8 percent) of the 34 images, and the mean weighted kappa for each expert compared with all others was between 0.21 and 0.40 (fair agreement) in seven (31.8 percent) experts, and 0.41 and 0.60 (moderate agreement) in 15 (68.2 percent). In the two-level categorization, all experts who provided a diagnosis agreed in seven (20.6 percent) of the 34 images, and the mean kappa for each expert compared with all others was between zero and 0.20 (slight agreement) in one (4.5 percent) expert, 0.21 and 0.40 (fair agreement) in three (13.6 percent), 0.41 and 0.60 (moderate agreement) in 12 (54.5 percent), and 0.61 and 0.80 (substantial agreement) in six experts (27.3 percent).

The authors conclude that agreement of plus disease diagnosis is imperfect. This finding may have implications for clinical ROP management and continued refinement of the international ROP classification system, as well as potential diagnostic standardization through implementation of telemedicine systems and development of computer-based image analysis algorithms.

Heterozygous TULP1 Mutations in Severe Early-Onset Retinitis Pigmentosa
July’s Archives

Den Hollander et al. examined a family with five individuals affected by autosomal recessive retinitis pigmentosa.

A genome-wide linkage scan suggested linkage to a region on chromosome 6 encompassing the TULP1 gene. Mutation analysis of TULP1 identified novel compound heterozygous mutations (p.Arg482Trp and p.Leu504fsX140) in the five affected family members. They all had a severe retinal dystrophy with a history of nystagmus, low visual acuity and nyctalopia since infancy. The scotopic and photopic responses were nonrecordable on electroretinography.

Clinical and molecular genetic characterization of autosomal recessive retinitis pigmentosa may help to provide a more accurate prognosis in individual patients. This study confirms that TULP1 mutations cause a severe, early-onset form of autosomal recessive retinitis pigmentosa.

Infliximab for Refractory Inflammatory Disease
July’s Archives

In this study by Sobrin et al., 27 patients with noninfectious ocular inflammatory disease refractory to traditional steroid and immunomodulatory therapy were treated with intravenous infliximab, a monoclonal antibody inhibitor of tumor necrosis factor-alpha. Clinical response, or resolution of inflammation, was assessed by medical record review in these patients with scleritis, uveitis or cicatricial pemphigoid.

Twenty-one patients experienced sustained improvement in inflammation, with 16 able to decrease other immunomodulatory medications they were taking, and four able to stop all other such medications. Three patients with scleritis remained relapse-free even after stopping infliximab infusions. At 12 months of therapy, half of the eyes involved in these 27 patients had improvement of visual acuity of two or more Snellen lines. An adverse event required discontinuation of infliximab in one patient.

The authors conclude that infliximab can be useful in the care of patients with ocular inflammatory disease that is otherwise resistant to more conventional immunosuppressive and corticosteroid therapy, and that the incidence of adverse events is low.

Apolipoprotein E Gene Polymorphisms and Retinal Vascular Signs
June’s Archives

Liew et al. examined if apolipoprotein E (APOE) gene polymorphisms, which are associated with large vessel atherosclerosis and retinal diseases such as age-related macular degeneration, are associated with retinal vascular signs such as focal narrowing, arteriovenous nicking and retinopathy in persons without diabetes.

More than 10,000 participants aged 49 to 73 from the Atherosclerosis Risk in Communities Study each had retinal photographs taken in one randomly selected eye.

Photographs were graded for presence of retinal vascular signs using a standardized protocol. DNA from blood samples was analyzed for common APOE alleles. After adjusting for age, sex, systolic blood pressure, total serum cholesterol, triglycerides and other covariates, APOE e4 was associated with nondiabetic retinopathy in white and black individuals. Other retinal vascular signs were not associated with APOE polymorphisms.

The authors conclude that APOE polymorphisms have little effect on retinal vascular signs. APOE e4 may slightly increase risk of retinopathy in persons without diabetes.

Blood Pressure, Arterial Stiffness and Glaucoma
June’s Archives

Hulsman et al. investigated the associations among blood pressure, arterial stiffness and open-angle glaucoma.

A total of 5,317 participants from the population-based Rotterdam Study were included in this cross-sectional study. Cases were classified into high-tension open-angle glaucoma and normal-tension open-angle glaucoma, according to an IOP of greater than 21 mmHg or less than or equal to 21 mmHg. Pulse pressure was calculated as the difference between systolic and diastolic blood pressure; diastolic perfusion pressure was the difference between diastolic blood pressure and the intraocular pressure; and indicators of arterial stiffness were carotid-femoral pulse wave velocity and carotid distensibility. Associations were adjusted for age, sex, body mass index, smoking, diabetes mellitus, serum cholesterol level and blood pressure-lowering treatment.

Systemic hypertension was not significantly associated with any open-angle glaucoma. However, in persons treated for systemic hypertension, low diastolic perfusion pressure (less than 50 mmHg) was inversely associated with normal-tension open-angle glaucoma (odds ratio per standard deviation, 0.25) and positively associated with high-tension open-angle glaucoma (odds ratio, 4.68).

In participants with a higher pulse pressure, a higher prevalence of high-tension open-angle glaucoma was found (odds ratio, 1.32). Participants within the lowest tertile of carotid distensibility had a higher prevalence of high-tension open-angle glaucoma (odds ratio, 2.84).

The authors conclude that high-tension open-angle glaucoma is associated with high pulse pressure, possibly with increased carotid arterial stiffness, and, only in persons treated for systemic hypertension, with low diastolic perfusion pressure. In persons treated for systemic hypertension, normal-tension open-angle glaucoma was associated with high diastolic perfusion pressure, whereas the association between normal-tension open-angle glaucoma and low diastolic perfusion pressure was inverted.

Topical Bevacizumab Therapy for Corneal Neovascularization
June’s Archives

DeStafeno and Kim examined the effect of topically applied anti-VEGF therapy using bevacizumab on human corneal neovascularization.

Two patients with corneal neovascularization unresponsive to topical corticosteroid therapy were enrolled. All topical therapies were discontinued six months prior to initiation of bevacizumab therapy. Each subject received topical bevacizumab therapy four times a day for a 25-day duration. The final formulation was 1 percent bevacizumab (10 mg/ml) with 0.01 percent benzalkonium chloride (0.1 mg/ml) and a pH of 6.2.

Patients were examined at three days, one week, two weeks and 25 days after therapy was initiated. Ocular irritation and hyperemia were recorded. Slit-lamp examination, photography and systemic blood pressure were recorded at each visit.

A marked reduction in both superficial and deep stromal corneal neovascularization was demonstrated both clinically and photographically. No adverse ocular effects, including conjunctivitis, epitheliopathy or burning upon installation, were noted. The patients did not report any systemic adverse events and systemic blood pressure remained at baseline.

The authors conclude that topical bevacizumab therapy could potentially provide a safer and more effective alternative or adjunct to conventional therapies in treating corneal neovascularization without the potential adverse effects. Although the long-term safety and efficacy of this therapy remain to be determined, the initial impressive short-term response and high tolerance to topical use offer encouraging results for the potential role of topical anti-VEGF medications in treating corneal diseases associated with neovascularization.

Antimicrobial Susceptibility of Fusarium, Aspergillus and Other Filamentous Fungi Isolated From Keratitis
June’s Archives

Lalitha et al. used macrobroth dilution to test the susceptibility of 90 isolates from filamentous fungal keratitis cases at Aravind Eye Hospital in South India for susceptibility to amphotericin B, natamycin, caspofungin, itraconazole, voriconazole and posaconazole. The minimum inhibitory concentration (MIC) median and 90th percentile were determined.

The isolates included 41 Aspergillus, 38 Fusarium and 11 others. The triazoles and caspofungin had the lowest MICs against Aspergillus. Voriconazole, amphotericin and posaconazole had the lowest MICs against Fusarium. At the concentrations tested, none of the Fusarium isolates were inhibited by itraconazole or caspofungin. Amphotericin B had significantly lower MICs compared with natamycin, but after correcting for the typical prescription dose, natamycin was superior.

No one agent was most effective, but voriconazole and other triazoles demonstrated the broadest spectrum.

Ophthalmology summaries are written by Lori Baker Schena and edited by John Kerrison, MD. 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

Exploring Combinations of Vancomycin, Amikacin and Dexamethasone In Vitro

In this study, Hui et al. set out to examine the possible precipitation process of a commonly used antibiotic regimen—vancomycin and amikacin—as well as the anti-inflammatory agent dexamethasone in the treatment of endophthalmitis. They explored this through the use of checkerboard titration and equilibrium dialysis in vitreous medium, with the three medications prepared in normal saline (NS) and balanced salt solution plus (BSS plus) separately.

Amikacin showed no measurable loss in NS or BSS plus, either alone or when mixed with vancomycin or dexamethasone. Vancomycin demonstrated minimal loss in BSS plus, both alone and when mixed with amikacin or dexamethasone. Finally, at 48 hours, dexamethasone showed a median loss of 16 percent when incubated alone in NS and 15 percent in BSS plus. When mixed with either of the other two agents, it showed a median loss of 13 percent with vancomycin and 12 percent with amikacin at 48 hours.

A previous finding by the authors that both ceftazidime and ciprofloxacin precipitated in vitreous led the authors to conclude that the vancomycin-amikacin regimen represents the preferred treatment choice.

Genetic Link to Progression of Age-Related Macular Degeneration
Journal of the American Medical Association

Seddon et al. have found that common polymorphisms in the genes CFH and LOC387715 are independently related to the progression of age-related macular degeneration, thus perhaps offering prognostic potential in identifying patients who may be highly susceptible to developing advanced stages of this disease.

The authors conducted a prospective analysis of 1,466 Caucasian individuals participating in the Age-Related Eye Disease Study (AREDS), of whom 281 progressed to the late stages of AMD. They found that both the CFH Y402H and LOC387115A69S were independently related to the progression of AMD from early and intermediate stages to advanced stages—all controlling for demographic factors, smoking, body mass index and AREDS vitamin-mineral treatment. The risk of AMD in the presence of all adverse factors, including both risk genotypes, smoking and a body mass index of greater than 25, increased nineteenfold.

The authors foresee a time when risk profiles on these patients may include genetic and environmental factors. Automated Detection in Diagnosis of Diabetic Retinopathy

Automated Detection in Diagnosis of Diabetic Retinopathy
Investigative Ophthalmology & Visual

Can a learning-based, automated computer program detect exudates and cotton-wool spots in digital color fundus photographs and differentiate them from drusen? Findings from a study by Niemeijer et al. indicate that this technology can, in fact, work.

The authors utilized 300 retinal images from one eye of each of 300 patients included in a telediagnosis database. One hundred patients had previously been diagnosed with bright lesions (i.e., exudates and cotton-wool spots) and 200 had not. The machine’s findings were then compared with findings from human experts. The results showed that the machine-learning algorithm described in the study was capable of detecting exudates, cotton-wool spots and drusen, and differentiating among them.

The area under the receiver-operator characteristic curve of 0.95 demonstrated that this proof-of-concept system has sensitivity and specificity approaching that of retina experts.

Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.