When a person experiences vision impairment or declining health, caregiving typically falls to a family member, most often a spouse. This increased burden can sometimes cause burnout, stress, and illness in the caregiver.

A study published in the Winter 2011 edition of the journal Insight: Research and Practice in Visual Impairment and Blindness explores levels of burden and depression reported by caregivers. This study focused on people over the age of 65 with blindness, deafness, or both impairments, and the spouse or partner who serves as caregiver.

Twenty-five spouses were recruited for this study. Of the partner with sensory impairment, 6 had vision loss, 8 had hearing loss, 5 had dual-sensory loss, and 6 were control participants with no sensory loss.

The investigators expected that spouses whose partners had sensory loss would report higher levels of both burden and depression compared to the control group. But this was not the case. In fact, the one comparison that did show a significant difference indicated that those in the control group, with no sensory loss, experienced a greater feeling of burden than those in the hearing-impaired group!

The researchers were surprised by this unexpected finding. It suggests that many couples can adjust very well when one partner suffers vision or hearing loss. This is wonderful testimony to the strength of many marriages.

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There is evidence of increased risk of stroke and hemorrhage associated with intravitral Lucentis therapy of AMD, and insufficient evidence of Avastin safety, according to a major review of the literature.

The current study was a systematic review in order to compare adverse effects (AE) and the reporting of harm in randomized controlled trials (RCTs) and non-RCTs evaluating intravitreal Lucentis and Avastin in AMD. Studies which compared Avastin or Lucentis as monotherapy with any other control group were included.

The 2 year results of phase III trials evaluating Lucentis show that the rates of serious ocular AE were low (less than or equal to 2.1%) but indicate major safety concerns. A possible risk with regard to thromboembolic events (blood clots) and a significant increase in non-ocular hemorrhage, such as bleeding stomach ulcers, were also noted.

In contrast to Lucentis trials, the studies evaluating Avastin are of limited value. The main shortcomings are small sample sizes and an apparent lack of rigorous monitoring for AE. A critical assessment of the large number of published case series evaluating Avastin shows that no reliable conclusions on safety can be drawn. Therefore, any perception that intravitreal Avastin injections are not associated with major ocular or systemic AE are not supported by reliable data.

The researchers conclude that Avastin studies show too many methodological limitations to rule out any major safety concerns. Higher quality evidence from Lucentis trials suggests risks for ocular and systemic hemorrhage which warrants further investigation.

WHAT IT MEANS TO YOU: It would be a mistake to assume that the risks associated with intravitreal Avastin use are the same as those for Lucentis. Chemically, the two molecules are very different. The vigorous studies that have been conducted on Lucentis reveal that there are few significant risks associated with its use. It is tempting to assume that the same is true of Avastin, but in the absence of research evidence to back this up, we are simply hoping for the best. Experience with the use of Avastin to treat cancer has found that it is associated with few serious systemic adverse effects in these patients. However, serious ocular adverse effects such as glaucoma and uveitis have been reported much more often following intravitreal Avastin use than with Lucentis. Ongoing trials comparing intravitreal Avastin and Lucentis, such as CATT, should shed some light on the relative safety of these two drugs.

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A new study finds that Lucentis (ranibizumab) significantly improves the vision of patients with very poor baseline visual acuity secondary to neovascular AMD.

Previous studies have produced conflicting results regarding the benefit of anti-VEGF therapy for patients with low vision; with some study finding no benefit, and others finding a significant benefit.

In this study, patients treated with Lucentis because of wet AMD with VA of 20/200 or less and with a follow-up period of at least 6 months were retrospectively reviewed. Data on a total of 135 patients were analyzed.

Median months of follow-up was 14 (range 6-27), and median number of treatments was 5.6 (range 2-14). There was a significant increase in median VA after treatment (median: 0.98 logMAR, range 0-2) compared to VA before treatment (median: 1.1 logMAR, range 1-2). There was a significant correlation between initial VA and final VA. 54% of the patients improved in VA, 23% maintained their vision, and 23% lost vision. No correlations regarding changes in VA and CNV subtype, total lesion size and/or presence of PED were observed.

This study suggests that Lucentis may improve VA in patients with low vision. The researchers concluded that patients with wet AMD and low vision may benefit from Lucentis therapy.

WHAT IT MEANS TO YOU: There is some controversy regarding the benefit of anti-VEGF therapy for patients with very poor vision and/or long-standing maculopathy. It is thought that many of these patients may have scarring of the macula that could prevent them from responding favorably to treatment. A few small studies have been performed on this patient population with mixed results. Some studies find a significant vision benefit while others have not. This is likely due to differences in how the patient population was selected for inclusion in the study. For example, the current study simply used visual acuity as a criteria for inclusion. Studies that use criteria that are more reflective of the duration of disease, such as amount of subretinal fibrosis, are likely to yield very different results. Until better studies provide guidance on which patients with low vision are most likely to benefit from therapy, clinicians will have to make this decision on a case-by-case basis using antidotal experience for guidance.

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A questionnaire that assesses a patient's subjective perception of metamorphopsia correlates well to metamorphopsia measured using two clinical tests.

There are several new clinical tests for metamorphopsia (visual distortion), such as the M-CHARTS test that can quantify the degree of metamorphopsia, and the PreView PHP computer test based on the hyperacuity phenomenon.

By obtaining the patient's subjective impression of metamorphopsia with a questionnaire, eye doctors can compare the severity assessed by clinical tests with the level of subjective metamorphopsia evaluated by the questionnaire

The researchers designed a 10-item questionnaire focusing on the symptoms of metamorphopsia. The questionnaire was given to 39 patients with epiretinal membrane (ERM), 22 patients with macular hole, 19 patients with AMD, and 51 healthy controls. These patients were then tested with both the M-CHARTS and PHP clinical tests.

The questionnaire score significantly correlated to the M-CHARTS score in ERM but not in patients with macular hole, and to the PHP result in AMD but not in ERM. M-CHARTS showed better sensitivities than PHP in both ERM (89% vs. 42%) and AMD (74% vs. 68%) and better specificity (100% vs. 71%) in healthy controls.

These results showed that patients' subjective perceptions of metamorphopsia evaluated by the questionnaire correlated well with the assessments by M-CHARTS and PHP in patients with macular diseases.

The researchers conclude that the metamorphopsia questionnaire can supplement PHP in patients with AMD and can supplement M-CHARTS in patients with ERM and AMD.

WHAT IT MEANS TO YOU: Many patients will remain unaware of significant changes in their vision because they fail to take the time to check how well each eye can see when one eye is covered. It is only by covering one eye that you can truly determine how well each eye is working because when both eyes are open a stronger eye will compensate for a weaker eye. This questionnaire is of value if it encourages patients to think about and check their vision on a regular basis. The normal daily experiences of reading, looking at peoples faces, and seeing telephone poles can be very useful in assessing the quality of your vision without the need for specialized tests, such as the Amsler grid. Any change in your vision should be reported to your eye doctor immediately. But it is extremely important that you close one eye at a time to be certain that changes are not overlooked.

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Utilizing a treat-and-extend treatment regimen for Avastin (bevacizumab) or Lucentis therapy proved visually efficacious as well as time- and cost-efficient among patients with neovascular AMD, a speaker said at the Macula 2011 meeting.

While visual outcomes and recurrence rates were similar for patients who received Lucentis or Avastin, Avastin therapy cost less, Omesh P. Gupta, MD, said at Macula 2011.

Dr. Gupta presented data from 166 eyes of 159 patients in a retrospective case series comparing visual outcomes, number of injections and medical costs of therapy in patients who received Lucentis or Avastin. Mean follow-up was 1.5 years.

Patients were treatment-naive at the start of therapy and received monthly injections until seen as "dry" on OCT assessment. Treatment intervals were extended by 2 weeks at a time unless exudation was seen on OCT.

Visual outcomes were similar between the two arms of the study. At 1 year, 32% to 35% of patients gained at least three lines. The mean period of extension between the two arms was statistically significant, Dr. Gupta said, with Avastin treatments extending longer.

The treat-and-extend regimen was linked to significantly fewer patient visits, fewer injections and lower medical costs compared to all phase-3 trials (such as MARINA and ANCHOR).

Mean number of injections and overall cost were greater in the Lucentis group, Dr. Gupta said.

"Significant cost savings can be achieved with treating patients with bevacizumab compared to ranibizumab," he said.

WHAT IT MEANS TO YOU: The argument in favor of using Avastin over Lucentis is almost always economic. Because Avastin is much cheaper than Lucentis, patients and their insurance provider can save lots of money by using Avastin. However, the "treat and extend" dosing strategy reveals another potential benefit of Avastin - its longer half-life. There are several studies indicating that Avastin may have a longer duration of action than Lucentis. The treat and extend approach is designed to take maximum advantage of the drug's duration of action by titrating the injections (and office visits) to the longest possible period for each patient. This study finds that, on average, patients on Avastin could go longer between injections than patients on Lucentis.

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There was no significant difference in clinical outcome following two different RPE transplantation techniques (RPE-suspension technique and the RPE-choroid-sheet technique) for the treatment of AMD.

Transplantation of RPE (maculoplasty) was introduced more than two decades ago, and is useful in the treatment of advanced AMD, geographic atrophy and/or anti-VEGF non-responders.

Fourteen consecutive patients with advanced exudative AMD were randomly assigned to RPE-choroid sheet transplantation (group 1) or RPE cell-suspension transplantation (group 2).

A gain of three or more lines in BCVA at 24 months was found in two patients in group 1 and in one patient in group 2, whereas a loss of vision of three or more lines occurred in one patient in each group.

This randomized study found that transplantation of RPE-choroid sheet and RPE-cell suspension enabled the maintenance of distance BCVA or in the best cases the restoration of foveal function in patients who were nonresponders or were not candidates for other treatments.

The functional outcome was comparable between both groups in this series and quite similar to the results reported in the literature.

In conclusion, transplantation of RPE offers an alternative approach in advanced AMD, and is also suitable for geographic AMD and other degenerative retinal diseases. However, the functional results with RPE transplantation techniques do not approach the levels of outcome seen with anti-VEGF treatment.

WHAT IT MEANS TO YOU: Despite the great success of anti-VEGF therapy for wet AMD, there remains a need for alternative treatments for those patients that do not respond to anti-VEGF therapy, or have dry AMD. Surgical treatments, such as maculoplasty, are continuing to evolve. This study finds that maculoplasty is able to maintain the vision of most patients with advanced AMD that undergo this procedure.

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A deficiency of an enzyme that degrades RNA, known as DICER1, may cause dry age-related macular degeneration (AMD).

In patients with dry AMD extensive atrophy of the retinal pigment epithelium (RPE) leads to severe vision loss and is termed geographic atrophy (GA).

In this study researchers identify a deficiency of an enzyme that degrades RNA in patients with GA. The enzyme, known as DICER1, is responsible for removal of excess RNA that can accumulate within a cell and become toxic. RNA is the chemical messenger within cells that transports genetic information from DNA to sites in the cell that turn this information into proteins.

The excess RNA, known as Alu elements, arises due to the presence of repetitive elements in the human genome that have no known purpose. Alu elements make up a surprisingly large portion - about 11 percent by weight - of the human genome, comprising more than 1 million sequences. However, their function is unknown, so they have been called "junk" DNA or part of the "dark" genome.

This researchers found very low levels of the enzyme DICER1 in the RPE of human donor eyes with GA. Experimentally decreasing DICER1 levels in laboratory cultures of human and mouse RPE cells resulted in elevated levels of Alu RNA elements within the cells, confirming a cause and effect relationship between low DICER1 levels and elevated Alu RNA levels.

The scientists then experimentally decreased DICER1 levels in the RPE of laboratory mice and found that this leads to RPE degeneration. Finally, they discovered that RPE degeneration can be prevented in DICER1-deficient mice by treatments that either increase DICER1 levels or decrease Alu RNA levels.

It was reported that the researchers are preparing to start clinical trials of dry AMD treatments based on their discovery.

WHAT IT MEANS TO YOU: This exciting discovery represents a potential breakthrough in our understanding of dry AMD. This landmark study clearly demonstrates a cause and effect relationship between toxic levels of RNA caused by DICER1 deficiency and geographic atrophy. It may also lead to treatments for dry AMD, but it remains to be seen whether treatments that were effective in laboratory mice will work in humans. Nonetheless, this study provides strong evidence for a biologically plausible mechanism for geographic atrophy. Without understanding the mechanism behind a disease, all attempts at treatment are really just "shots in the dark". Now it may be possible to tailor treatments specifically for the underlying defect that gives rise to AMD. That could lead to real progress in combating this disease.

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The North East Treatment Advisory Group (NETAG) has produced an appraisal of Avastin and Lucentis in the management of macular edema secondary to retinal vein occlusion and decided that as-needed Avastin is recommended for use within NHS North East as this regimen is considered a more cost-effective treatment option in RVO compared with Lucentis. The report acknowledges that the overall quality of Avastin evidence is lower than that for Lucentis, with most studies being relatively small and without a control group. Few were prospectively conducted. Neither Avastin nor Lucentis is currently licensed in Europe for the treatment of macular edema secondary to retinal vein occlusion.

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The onset of wet AMD occurs more often during the winter months than during the summer months, according to a study published in the February 2011 edition of Acta Ophthalmologica. Patients with new onset wet AMD attending a retina clinic between July 2006 and June 2008 were identified. A total of 366 patients were included in the analysis. 160 patients (44%) presented during summer months (May-October), while 206 patients (56%) presented during winter months (November-April). The difference between the two groups was statistically significant. The researchers identified a number of reasons why wet AMD may have a higher incidence in the winter months. Cardiovascular disease and hypertension are risk factors for AMD, and both have a seasonal variation with a peak in winter months. A second possible reason relates to sunlight. The relationship between light and AMD remains controversial. If sunlight is a trigger for AMD, why was there a higher incidence in winter? This may be because of a time lag between retinal damage and the development of symptomatic wet AMD.

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Researchers have found a relationship between diabetes mellitus and early AMD in Korean adults, according to a study published in the February edition of Archives of Ophthalmology. Other than age, the epidemiologic risk factors most consistently associated with AMD are cardiovascular risk factors. Smoking, elevated total serum cholesterol, higher body mass index (BMI), and hypertension have been associated with AMD in some but not all studies. Other cardiovascular risk factors, including diabetes, have not been consistently associated with AMD in large population-based samples. This study included 3008 participants aged 50 to 87 years. There were 88 subjects with early AMD and 315 subjects with diabetes mellitus. After adjusting for age, sex, current smoking, obesity, and hypertension, significant association was found between diabetes mellitus and early AMD. Subjects with diabetes mellitus were more likely to have early AMD (odds ratio, 1.87) than were those without diabetes mellitus. The researchers conclude that there is a relationship between diabetes mellitus and early AMD in Korean adults 50 years and older.

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Several new devices designed to deliver drugs to the posterior pole may address the drawbacks of current technologies, according to a speaker at the Macula 2011 meeting. The ideal drug delivery device would be able to deliver multiple drugs to the vitreous cavity, subretinal space or suprachoroidal space without serious side effects, Mark Wieland, MD, said at Macula 2011. On Demand Therapeutics developed a novel drug delivery system that is inserted into the vitreous and activated using a standard laser. It has multiple reservoirs for various drugs and is hermetically sealed to preserve protein stability, Dr. Wieland said. According to Dr. Wieland, iScience has developed the world's smallest catheter, which injects proteins through the pars plana and into the suprachoroidal space. Delivering drugs to the suprachoroidal space may avoid the side effects of glaucoma and cataract and increase the duration of activity of the drug, he said. "Although these are intriguing approaches to delivering drugs to the posterior pole, it is clear that we have yet to develop the ideal drug delivery system," he said.

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