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November/December 2006

Journal Highlights

New Findings from Ophthalmology, AJO and Archives

December's Ophthalmology:

November's American Journal of Ophthalmology:

October's Archives of Ophthalmology:

Roundup of Other Journals:


Optic Disc Hemorrhage and Risk of Developing Glaucoma Ophthalmology
December’s issue

Current findings from the Ocular Hypertension Treatment Study indicate that careful review of optic disc photographs detects optic disc hemorrhages more frequently than does clinical examination.

Budenz et al. also found an association between optic disc hemorrhage and an increased risk of developing a primary open-angle glaucoma (POAG) end point. However, most eyes (86.7 percent) that developed a disc hemorrhage have not developed a POAG end point to date. This cohort involved 3,236 eyes of 1,618 participants who were studied to determine whether lowering IOP in ocular hypertension delayed or prevented POAG.

In light of the current findings, the authors recommend that optic disc hemorrhage be included in the decision matrix about initiating treatment in a patient with ocular hypertension. Because optic disc hemorrhages represent a strong predictive factor for development of POAG in ocular hypertension, the authors also suggest frequent monitoring for optic disc hemorrhages by careful examination of the optic disc and/or optic disc photography.

U.S. Costs for Correction of Distance Vision Impairment
December’s issue

Healthy People 2010, sponsored by the Department of Health and Human Services, has made reduction of visual impairment due to refractive errors a national priority.

Vitale et al. used utilization data from the 1999–2000 National Health and Nutrition Examination Survey, along with data from the Medical Expenditure Panel Survey and CMS, to estimate the cost of providing refractive correction to all Americans who need eyeglasses or other corrective lenses to achieve normal levels of distance visual acuity.

They found more than 110 million Americans could or do achieve normal vision with refractive correction. The annual direct cost of correcting distance vision impairment is estimated to be between $3.9 billion and $7.2 billion. For the $3.9 billion figure, $2.94 billion represents costs of glasses already purchased for which recurrent costs will be incurred, and $967 million represents the costs to provide an initial set of glasses. These cost estimates provide useful information in analyzing ophthalmic public health endeavors.

Association Between Cataract and Frailty in Older Americans
December’s issue

A study by Klein et al. involving 2,370 older members (99 percent of whom were Caucasian) of the Beaver Dam Eye Study at the 10-year examination mark demonstrates an association between three types of age-related cataract (nuclear, cortical and posterior subcapsular) and some measures of frailty, independent of visual acuity and systemic comorbidities.

The investigators found an association between nuclear cataract in men and slower gait time and poorer frailty index. Cortical cataract in women was associated with lower peak expiratory flow rate and in men with weaker handgrip strength and poorer frailty index. Finally, posterior subcapsular cataract in women was significantly associated with lower peak expiratory flow rate.

The authors conclude that cataract may be considered an indicator of general decline in function in older adults, independent of visual acuity.

Consequently, physicians should keep in mind that older persons with cataract may benefit from functional assessment and assistance.

Oral Antiviral Therapy Effective for Acute Retinal Necrosis
December’s issue

In a small, retrospective case series by Emerson et al., four patients (six eyes) with indolent acute retinal necrosis (ARN) were successfully treated with oral rather than the conventional intravenous antiviral therapy.

Oral therapy included valacyclovir (1 g three times daily) and famciclovir (500 mg three times daily) for five weeks to three months. Patients also received topical and oral corticosteroids. With this approach, symptoms and visual acuity improved within two weeks to one month in three of four patients treated.

These findings suggest that patients with peripheral indolent ARN may benefit from oral antiviral therapy. However, the authors recommend further study to determine whether valacyclovir or famciclovir is as rapid and effective as IV acyclovir for initial treatment of this condition. In the interim, the standard of care, IV antiviral therapy, should be used for patients with the typical presentation of ARN, including rapidly progressive inflammation involving the peripheral retina.

Differentiating Cerebral Venous Sinus Thrombosis From Idiopathic Intracranial Hypertension
December’s issue

While cerebral venous sinus thrombosis (CVST) is considered uncommon, the clinical presentation overlaps with idiopathic intracranial hypertension (IIH). According to a report by Lin et al., it is crucial to differentiate the two conditions because CVST is typically treated with anticoagulation, and IIH with diuretics. In addition, apart from headache and visual loss, there are typically no neurologic complications of IIH, while CVST can cause stroke and death.

For this study, researchers conducted a chart review of 131 patients with papilledema from three tertiary care neuro-ophthalmology centers. They found that the occurrence of CVST was 9.4 percent in patients with presumed IIH. These results suggest that it is prudent to perform magnetic resonance venography (MRV) in combination with MRI on all patients with suspected IIH, as CT or MRI alone is not adequate to exclude CVST. The authors also suggest a prospective study to confirm these findings.


Endophthalmitis Despite Prophylactic Gatifloxacin or Moxifloxacin
American Journal of Ophthalmology
November’s issue

Routine use of prophylactic antibiotics prior to cataract surgery is practiced by most ophthalmologists despite the lack of definitive research findings and the cost of these medications.

Deramo et al. studied the use of prophylactic fourth-generation fluoroquinolone antibiotics, gatifloxacin and moxifloxacin, and bacterial sensitivity in cases of acute postoperative endophthalmitis following cataract surgery in a retrospective, consecutive, observational case series.

Forty-two eyes of 42 patients with acute endophthalmitis occurring within six weeks after cataract surgery were identified over a two-year time interval. Thirty-one of 42 eyes (74 percent) were treated with perioperative gatifloxacin or moxifloxacin and 24 eyes (57 percent) were continuously treated with one of these antibiotics at the time of diagnosis of endophthalmitis. Nineteen eyes (45 percent) had a positive bacterial culture.

The most frequent organism isolated was coagulase-negative Staphylococcus. Sensitivities were performed for 14 gram-positive organisms, and sensitivities to ciprofloxacin (50 percent), ofloxacin (44 percent), levofloxacin (46 percent), gatifloxacin (38 percent) and moxifloxacin (38 percent) were noted. Five organisms were resistant to gatifloxacin and moxifloxacin with a minimum inhibitory concentration of 8 µg/ml. All gram-positive organisms were sensitive to vancomycin. Median visual acuity improved from hand motions to 20/40 at last follow-up.

Acute endophthalmitis can develop after cataract surgery despite the prophylactic use of fourth-generation fluoroquinolone antibiotics. Gram-positive organisms causing acute endophthalmitis are frequently resistant to all fluoroquinolones, including a significant number of cases resistant to gatifloxacin and moxifloxacin.

Toxicity of Indocyanine Green Dye in Macular Hole Surgery
American Journal of Ophthalmology
November’s issue

The toxicity of indocyanine green dye has been implicated in some prior articles. Ferencz et al. evaluated the possible toxicity of indocyanine green dye (ICG) in macular hole surgery by comparing functional results after successful surgeries performed with and without staining in a prospective observational case series.

Three eyes of 29 patients with idiopathic macular hole underwent pars plana vitrectomy, with peeling of the internal limiting membrane (ILM). In 21 eyes (group A), ICG staining was used to visualize the membrane; in nine eyes (group B), no dye was applied. Pre- and postoperative examinations (at three, six, 12 and 20 months) included visual acuity (VA) (Snellen chart), slit-lamp biomicroscopy, multifocal electroretinography (mfERG) and optical coherence tomography.

The macular hole was closed in all patients. At 20 months, VA improvement (logarithm of minimal angle of resolution units) compared with baseline was more pronounced in group B (P < 0.001) than in group A (P = 0.022); VA was also better for group B compared directly to group A (P = 0.048). For mfERG, preoperative responses were subnormal. Postoperatively, responses initially decreased, but at 20 months, improvement was seen in both groups (P < 0.001). When data from the groups were compared at 20 months, significantly greater mfERG improvement was found in group B in both central and perimacular areas (P < 0.001).

The significantly better outcome without staining suggests dye toxicity. Alternative internal limiting membrane visualization substances with fewer adverse effects (trypan blue, triamcinolone) may be preferable.

Doses of Triamcinolone Acetonide Compared for Diffuse Diabetic Macular Edema
American Journal of Ophthalmology
November’s issue

Although not approved for this usage, intravitreal triamcinolone has been used extensively for many vitreoretinal diseases.

Audren et al. compared the effects of 4 vs. 2 mg intravitreal triamcinolone acetonide (TA) injection for diabetic macular edema in a prospective, interventional case series.

Thirty-two patients with diabetic macular edema unresponsive to laser photocoagulation were randomly assigned to receive 4 or 2 mg intravitreal TA in one eye (16 patients in each group).

The main outcome was central macular thickness (CMT) measured by optical coherence tomography at four, 12 and 24 weeks. Secondary outcomes were gain in Early Treatment Diabetic Retinopathy Study (ETDRS) scores, intraocular pressure, cataract progression and duration of effect.

Before injection, mean CMT was 564.5 µm in the 4-mg group and 522.9 µm in the 2-mg group.

At four, 12 and 24 weeks after injection, it was 275 µm, 271 µm and 448 µm, respectively, in the 4-mg group, and 267 µm, 289 µm and 394 µm, respectively, in the 2-mg group.

At no time was the difference in CMT between both groups statistically significant (P > 0.3). The between-group differences in the gain in the ETDRS score and in IOP were not statistically significant either. Diabetic macular edema recurred after a median period of 20 weeks vs. 16 weeks in the 4- and 2-mg groups, respectively (P = 0.11).

In the short term, intravitreal injection of 4 or 2 mg TA did not have different effects on CMT, visual acuity or IOP.

Topical Ocular Hypotensive Medication and Lens Opacification
American Journal of Ophthalmology
November’s issue

Herman et al. from the Ocular Hypertensive Treatment Study (OHTS) group report further information from the study.

Data from this multicenter clinical trial were used to determine whether topical ocular hypotensive medication is associated with refractive changes, visual symptoms, decreased visual function or increased lens opacification.

The medication and observation groups of OHTS were compared during 6.3 years of follow-up with regard to the rate of cataract and combined cataract/ filtering surgery, and change from baseline in visual function, refraction and visual symptoms. An assessment of lens opacification was done using the Lens Opacities Classification System III (LOCS III) grading system.

An increased rate of cataract extraction and cataract/filtering surgery was found in the medication group (7.6 percent) compared with the observation group (5.6 percent). The medication and observation groups did not differ with regard to changes in Humphrey visual field mean deviation, Humphrey visual field foveal sensitivity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, refraction and visual symptoms. For the medication and observations groups, LOCS III readings were similar for nuclear color, nuclear opalescence and cortical opacification. There was a borderline higher mean grade for posterior subcapsular opacity in the medication group (0.43) compared with the observation group (0.36) (P = 0.07).

Idiopathic Sclerosing Orbital Inflammation
Archives of Ophthalmology
October’s issue

Hsuan et al. reviewed all cases of idiopathic sclerosing orbital inflammation from five regional orbital centers.

Thirty-one patients with histologically confirmed idiopathic sclerosing orbital inflammation are described. The clinical presentations, investigations, treatments and outcomes were reviewed. The presenting symptoms and signs reflected the anatomical location of the disease within the orbit. There was a predilection for the superolateral and apical regions. A good response to oral prednisolone was seen in a third of patients, with a trend between duration of disease and response to prednisolone. No specific second-line immunosuppressive agent was identified. The results of radiotherapy were generally poor. Surgery was of benefit in advanced disease.

The authors conclude that early diagnosis and adequate immunosuppression before established fibrosis has occurred may allow regression of the disease.

Dacryoadenitis Associated With Acanthamoeba Keratitis
Archives of Ophthalmology
October’s issue

Tomita et al. report the incidence of dacryoadenitis as a symptom associated with Acanthamoeba keratitis.

Twenty patients (21 eyes) with Acanthamoeba keratitis were retrospectively investigated for the incidence of dacryoadenitis diagnosed by clinical signs of lacrimal gland swelling and pain on pressure, computed tomography, MRI and histopathologic analysis. Eight eyes (38 percent) of eight patients had dacryoadenitis simultaneously with Acanthamoeba keratitis. Examination in two patients revealed moderate infiltration of lymphocytes and plasma cells in the lacrimal gland compatible with dacryoadenitis. No Acanthamoeba organisms were found in the lacrimal gland. Lacrimal gland swelling improved after a mean of 10 weeks (range: four to 17 weeks) in conjunction with symptoms of keratitis.

The authors say that since the possibility of direct invasion of the lacrimal gland by trophozoites cannot be ruled out, Acanthamoeba infection should be included in the differential diagnosis in dacryoadenitis.

Intraocular Pressure Variation During Weight Lifting
Archives of Ophthalmology
October’s issue

Vieira et al. examined the effect of bench press weight lifting in normal healthy subjects on IOP with and without the performance of a Valsalva maneuver.

Sixty eyes of 30 healthy subjects were tested using two exercise modes. Both eyes of each subject were enrolled so that the right and left eyes were chosen to evaluate modes I and II. In mode I, the subjects exhaled when lifting the weight and inhaled when lowering it, but at the last repetition, they kept holding their breath long enough for the examiner to obtain a reliable measurement. In mode II, subjects did not hold their breath at the last repetition, but continued to exhale while lifting the bar. In mode I, the IOP increased in 90 percent of subjects by a mean of 4.3 mmHg. An increase in IOP greater than 5 mmHg was found in 30 percent of those subjects. In mode II, the IOP increased in 62 percent of subjects by a mean of 2.2 mmHg. Six of those subjects (21 percent) exhibited an increase of at least 5 mmHg, and five (17 percent) showed a decrease in IOP.

The authors conclude that prolonged weight lifting could be a potential risk factor for progression of glaucoma. Intermittent IOP increases during weight lifting should be suspected in patients with normal-tension glaucoma who perform such exercises. Patients with normal-tension glaucoma should be questioned regarding a history of regular weight lifting.

Progression of Retinopathy and Risk Factors in African-Americans With Type 1 Diabetes
Archives of Ophthalmology
October’s issue

Roy et al. examined the six-year progression of diabetic retinopathy and associated risk factors among African-Americans with type 1 diabetes.

Four hundred and eighty-three African-Americans with type 1 diabetes who participated in the New Jersey 725 study were reexamined as part of a six-year follow-up.

Evaluation included structured clinical interview, seven standard retinal photographs and blood and urine assays. Retinopathy severity was determined via masked grading of the retinal photographs.

During the six-year period, 56.1 percent of patients showed progression of retinopathy, 15 percent progressed to proliferative retinopathy and 16 percent developed macular edema. At follow-up, glycemic control remained poor and prevalence of systemic hypertension (44 percent) was high.

At baseline, high-glycosylated hemoglobin and systemic hypertension were significant risk factors for progression of retinopathy, progression to proliferative disease and incidence of macular edema. Progression to proliferative retinopathy was significantly associated with baseline older age, renal disease and severity of retinopathy. Incidence of macular edema was significantly associated with baseline older age, low socioeconomic status, severity of retinopathy and total blood cholesterol.

Six-year progression of retinopathy is high in African-Americans with type 1 diabetes. Improving glycemic and blood pressure control is critical to reducing the ocular morbidity of diabetes in African-Americans.


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

Delayed vs. Immediate Antibiotic Use in Conjunctivitis
British Medical Journal
Published online July 17, 2006

A randomized, controlled trial by Everitt et al. demonstrated that delaying the prescription of antibiotics may be the optimal approach for managing acute conjunctivitis in the primary care setting.

The researchers divided adults and children with acute infective conjunctivitis into three treatment groups: immediate antibiotics with chloramphenicol eye drops (104 patients), no antibiotics (94 controls) and delayed antibiotics three days after diagnosis (109 patients). They found that while none of the approaches affected the severity of the symptoms, antibiotics did lessen the duration of moderate symptoms.

Specifically, the no-antibiotics group took 4.8 days for symptoms to subside, the immediate antibiotic group took 3.3 days and the delayed antibiotics group took 3.9 days.

In light of the question of whether a half-day’s reduction in moderate symptoms is worth prescribing immediate antibiotics compared with the possible benefits of delaying antibiotic use, the authors conclude that patients may be better served if the antibiotics prescription is delayed. Advantages include reduction of antibiotic use, symptom control similar to immediate prescribing and reduced recurrence for eye infections.

Congenital High Myopia and Regulation of Eye Size
Investigative Ophthalmology & Visual Science

According to Halfter et al., researchers have frequently linked congenital high myopia to mutations in genes encoding extracellular matrix proteins of the vitreous body (VB) and the inner limiting membrane (ILM). However, it remains a mystery as to why defective or missing VB and ILM proteins lead to an increase in eye size.

The authors used a chick embryo as a model to better understand the early regulation of eye size in congenital high myopia. To disrupt the ILM and VB, they injected collagenase into the eyes of the chick embryos. This injection led to the disruption of the ILM and the VB by digesting their collagen constituents. Once disrupted, the ILM and the collagen II fibrillar network failed to regenerate, even with continued synthesis of VB and ILM proteins.

These ILM and VB disruptions resulted in eye enlargement of 50 percent in four days, a phenomenon greatly reduced by reconstituting the ILM using mouse laminin-1 and alpha2-macroglobulin.

The authors conclude the ILM and the VB play key roles in the early regulation of eye size and speculate that the integrity of the vitreoretinal border is an important factor in preventing congenital high myopia.

Early Treatment of ROP Appears Beneficial
British Journal of Ophthalmology
Published online August 16, 2006

According to Good et al., two-year results from the Early Treatment for Retinopathy of Prematurity Study (ETROP) indicate that the benefits of earlier treatment for these patients continue through 2 years of age and are not offset by any known side effects caused by the earlier intervention.

In this study, infants with bilateral, high-risk, prethreshold ROP had one eye randomly assigned to treatment with peripheral retinal ablation, and the fellow eye managed conventionally.

These infants were later examined at age 2, with researchers looking for unfavorable structural outcomes such as a posterior retinal fold involving the macula, a retinal detachment involving the macula or retrolental tissue or “mass” obscuring the view of the posterior pole.

Using data from 339 of 374 surviving children, researchers found that unfavorable structural outcomes were reduced from 15.4 percent in conventionally managed eyes to 9.1 percent in early treated eyes. Ophthalmic side effects were similar in both treatment groups.

The authors conclude that earlier treatment improves the chance for long-term, favorable retinal structural outcome.

The authors plan to measure visual acuity with optotypes, contrast sensitivity and visual field studies in future examinations, when the children are old enough to cooperate with the testing procedures.


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