52 Retinoblastoma

Background

Retinoblastoma is the most common primary intraocular malignant tumour in children with an incidence of 1 in 15 000 live births.1 The average annual incidence of retinoblastoma of 10·9 per million for children younger than five years in the United States has remained stable from 1974 to 1985.2

Aetiology and diagnosis

Retinoblastoma is a familial disorder with an autosomal dominant inheritance. Approximately 60% of the patients are considered sporadic and 40% are heritable. White pupillary reflex, or leukocoria, is the most common presentation.3 Presence of intraocular calcium by ultrasonography or computed tomography is helpful in confirming the diagnosis.4

Retinoblastoma can be inherited as a familial tumour in which the affected child has a positive family history of retinoblastoma or as a non-familial (sporadic) tumour in which the family history is negative for retinoblastoma. Retinoblastoma can be classified in three different ways: familial or sporadic, bilateral or unilateral, and heritable or non-heritable (Table 52.1). Approximately 10% of newly diagnosed retinoblastoma cases are familial and 90% are sporadic.

Human retinoblastoma susceptibility gene (RB1) is located on chromosome 13 region 13–14. A review of published data indicates that mutations are distributed throughout the RB1 gene with no single mutational hotspot and are expected to alter pRB protein function.

Treatment options

In recent years there has been a trend away from enucleation,8 with the increased use of alternative globe conserving methods of treatment including external beam radiotherapy,9 plaque radiotherapy,10 laser photocoagulation,11 cryotherapy,12 transpupillary thermotherapy13 and chemotherapy.14

Since the 1990s chemoreduction has been increasingly used for the management of retinoblastoma to avoid external beam radiotherapy or enucleation.15,16 Chemoreduction

Table 52.1 Classification of retinoblastoma

implies usage of chemotherapy delivered intravenously to reduce the volume of intraocular retinoblastoma so as to make it amenable to focal therapy such as cryotherapy, thermotherapy or brachytherapy. Six-cycle chemoreduction using three agents (vincristine, etoposide and carboplatin) is generally prescribed.

Prognosis

Recent advances in the treatment of retinoblastoma have led to improved five-year survival rates of greater than 90% in the developed countries.2,17 However, in developing countries retinoblastoma is still associated with high mortality because it tends to present at a much more advanced stage.

The metastasis in retinoblastoma usually occurs within one year of diagnosis of retinoblastoma. If there is no metastatic disease within five years of retinoblastoma diagnosis the child is usually considered cured.18 Involvement of the central nervous system and hematogenous spread are the commonest sites of metastasis. Survival with metastatic retinoblastoma is generally limited to six months.18,19

Question

What is the role of chemoreduction in the management of retinoblastoma?

The evidence

We found no randomised controlled trials or metaanalyses relevant to this question.

Comment

Some small, uncontrolled prospective studies have reported the efficacy of chemoreduction in the management of retinoblastoma (Table 52.2). The extent of retinoblastoma is generally classified using a system proposed by Reese and Ellsworth.20 The retinoblastoma is staged from group I to group V on the basis of number, size, and the location of the tumours. The Reese-Ellsworth (RE) classification predicts the visual prognosis. Murphree and associates reported tumour control in 10 eyes with RE group I–IV disease and failure in seven eyes with extensive subretinal seeding and 18 eyes with RE group V disease.21 Kingston and associates were able to avoid enucleation in 12 of 20 eyes with RE group V, using chemoreduction and external beam radiotherapy.22 In a large prospective (non-randomised study) involving 158 eyes of 103 patients, all eyes showed initial tumour regression.23 About 50% of these eyes required external beam radiotherapy or enucleation. At five years, Reese-Ellsworth (RE) groups I–IV eyes showed better response than RE group V eyes. In RE group I–IV eyes, only 10% of the eyes required external beam radiotherapy and 15% necessitated enucleation, whereas in RE group V eyes almost 50% of the eyes failed therapy requiring external beam radiotherapy or enucleation.

Based on the available (non-comparative series) data it may be concluded that chemoreduction combined with adjuvant focal therapy offers about 50–90% probability of avoiding enucleation or external beam radiotherapy depending upon the severity of disease at initial presentation as judged by RE classification.

Chemoreduction is not without its problems, however. Recurrence of the neoplasm while on chemotherapy have been observed.24 Immediate complications related to transient bone marrow suppression requiring hospital admissions and intravenous antibiotics with consequent delay in examinations under anaesthesia are frequent.16,25 Risk of late complications such as drug-induced leukaemia have not yet been excluded.

Currently the choice of drug combinations, duration of chemotherapy and indications of chemoreduction are still under investigation. Therefore, it is recommended that chemoreduction therapy for retinoblastoma should only be offered as part of a clinical trial at a specialist centre. It is an arduous and prolonged task to monitor the progression of each tumour and access to all forms of focal adjuvant therapy should be available.

Despite recent advancement in retinoblastoma treatment, and the current trend in favour of measures to salvage the eye, enucleation is still a valid primary therapeutic option for advanced unilateral retinoblastoma.8 Primary enucleation offers a high cure rate of 90–95%.26 Metastasis may still develop in 5–10% of patients after primary enucleation for advanced unilateral retinoblastoma,2,17 and at a much

higher rate in the developing countries.27,28 With the availability of effective chemotherapy regimens for intraocular retinoblastoma,15,29 consideration of adjuvant chemotherapy to prevent metastasis in high-risk cases is appropriate. Nevertheless, the role of adjuvant postenucleation chemotherapy in retinoblastoma has yet to be clearly defined.30

There is disagreement over the histopathological prognostic factors that define high risk for developing metastasis. Although no RCTs or meta-analyses exist, several studies (mostly retrospective) have addressed this issue. The reported occurrence of anterior chamber seeding (7%), choroidal infiltration (12–23%), invasion of optic nerve, scleral infiltration (1–8%) and extrascleral extension (2–13%) varies between series18,31–35 It is now generally agreed, without strong evidence, that tumour invasion of the optic nerve at or beyond the lamina cribrosa, massive choroidal infiltration, scleral infiltration and extrascleral extension are risk factors predictive of metastasis18,28,35,36 However, the role and significance of anterior chamber seeding and isolated iris or ciliary body infiltration as risk factors for metastatic retinoblastoma remains

debatable.18,28,35,36

Question

What is the role of laser photocoagulation, cryotherapy, transpupillary thermotherapy and plaque radiotherapy in the management of retinoblastoma?

The evidence

We found no randomised controlled trial or meta-analysis comparing laser photocoagulation, cryotherapy, transpupillary thermotherapy and plaque radiotherapy in the management of retinoblastoma.

Comment

Retinoblastoma is a rare disease and it is not surprising that randomised trials comparing various treatment modalities are unavailable. The small case series are descriptive and provide information only on selected tumours that were specifically treated by a single modality. Such case series give information about the clinical situations where a given treatment would be indicated and the expected response rate.

Laser photocoagulation is an appropriate method of management in cases where the tumour is located posteriorly, the media is clear and the tumour is 3·0 mm or less in diameter and 2·0 mm or less in thickness without seeding into the adjacent vitreous.37

RE group I–II

Carboplatin Thermotherapy Avoid Enuc/EBRT 63

38

.,al etMurphree

Cryotherapy is indicated for anteriorly located tumours with clear media. Cryotherapy is effective for the tumours less than 2·5 mm in diameter and less than 1·0 mm in thickness without seeding into the adjacent vitreous.38 In a series of 138 tumours, 70% of tumours were cured with cryotherapy. There were few long-term ocular complications even with repeated cryotherapy.39

Transpupillary thermotherapy is generally used for relatively small tumours without associated vitreous or subretinal seeds and is used in conjunction with adjuvant chemotherapy. In a series of 188 tumours that had a mean tumour diameter of 3·0 mm and thickness of 2·0 mm, tumour regression was achieved in 86% with a recurrence rate of 14%. Larger tumours are at greater risk for complications such as focal iris atrophy and focal paraxial lens opacity because they require more intense therapy than smaller tumours.40

Plaque radiotherapy is highly effective in treating selected tumours with a high control rate. It can be used successfully even as a secondary treatment for tumours that have not been adequately controlled by other methods such as laser photocoagulation, cryotherpay or thermotherapy. In a series of 103 cases, for tumours with a mean diameter of 7 mm and the mean thickness of 4 mm, the control rate was 86%. The rate of tumour control was similar in the primary and secondary treatment groups.41

Question

Does post-enucleation adjuvant chemotherapy prevent metastasis in retinoblastoma?

The evidence

In the only prospective and randomised study by the Children’s Cancer Study Group comprising 14 patients with high-risk retinoblastoma treated with adjuvant chemotherapy, no significant difference in survival was demonstrable in comparison to the control group.42

Comment

Various retrospective studies on adjuvant chemotherapy do not offer strong evidence about its efficacy (Table 52.3). Other studies have also suggested an equivocal benefit or lack of benefit.43,44 On the other hand, several studies have indicated that adjuvant chemotherapy was beneficial.26,35,45,46 In a recent study, Uusitalo and associates concluded that adjuvant chemotherapy is necessary for patients with tumour extending to the surgical margin of the optic nerve and is likely to be beneficial in preventing metastasis in patients with tumour extending beyond the lamina cribrosa.47 Similarly, on the basis of retrospective data in patients with retinoblastoma manifesting histopathological high-risk characteristics, Honavar and associates reported a significant difference in the incidence of metastasis between the group that had received adjuvant chemotherapy (4%) and the group that had not (24%).46

Implications for research

It is evident that the major limitations of studies have been the rarity of the end-point (metastasis),26,42 lack of

comparable stratification for subgroup analysis,26,35,43,48 and the absence of a control group.26,43,44 A large randomised multi-centre prospective study is needed to identify specific high-risk characteristics in the presence of which postenucleation adjuvant chemotherapy is needed.46,47

References

1.Bishop JO, Madsen EC. Retinoblastoma: Review of current status.

Surv Ophthalmol 1975;19:342–66.

2.Tamboli A, Podgor MJ, Horm JW. The incidence of retinoblastoma in the United States: 1974 through 1985. Arch Ophthalmol 1990;108: 128–32.

3.Abramson DH, Frank CM, Susman M et al. Presenting signs of retinoblastoma. J Pediatr 1998;132:505–8.

4.Shields CL, Shields JA. Recent developments in the management of retinoblastoma. J Pediatr Ophthalmol Strabismus 1999;36:8–18.

5.Friend SH, Bernards R, Rogelj S et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986;323:643–6.

6.Lee WH, Bookstein R, Hong F et al. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 1987;235:1394–9.

7.Harbour JW. Overview of RB gene mutations in patients with retinoblastoma. Implications for genetic screening. Ophthalmology 1998;105:1442–7.

8.Shields JA, Shields CL, Sivalingam V. Decreasing frequency of enucleation in patients with retinoblastoma. Am J Ophthalmol 1989;108:185–8.

9.Hernandez JC, Brady LW, Shields JA et al. External beam radiation for retinoblastoma: results, patterns of failure, and a proposal for treatment guidelines. Intl J Rad Oncol Biol Phys 1996;35:125–32.

10.Shields JA, Shields CL, De Potter P, Hernandez JC, Brady LW. Plaque

radiotherapy for residual or recurrent retinoblastoma in 91 cases.

J Pediatr Ophthalmol Strabismus 1994;31:242–5.

11.Shields JA, Shields CL, Parsons H, Giblin ME. The role of photocoagulation in the management of retinoblastoma. Arch Ophthalmol 1990;108:205–8.

12.Shields JA, Parsons H, Shields CL, Giblin ME. The role of cryotherapy in the management of retinoblastoma. Am J Ophthalmol 1989;108:260–4.

13.Shields CL, Santos MC, Diniz W et al. Thermotherapy for retinoblastoma.

Arch Ophthalmol 1999;117:885–93.

14.Shields CL, Shields JA, Needle M et al. Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology 1997;104:2101–11.

15.Ferris FL, Chew EY. A new era for the treatment of retinoblastoma.

Arch Ophthalmol 1996;114:1412.

16.Friedman DL, Himelstein B, Shields CL et al. Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. J Clin Oncol 2000;18:12–17.

17.Anonymous. [National registry of retinoblastoma in Japan (1975–1982). The Committee for the National Registry of Retinoblastoma]. Nippon Ganka Gakkai Zasshi. Acta Soc Ophthalmol Jpn 1992;96:1433–42.

18.Kopelman JE, McLean IW, Rosenberg SH. Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation.

Ophthalmology 1987;94:371–7.

19.McCay CJ, Abramson DH, Ellsworth RM. Metastatic patterns of retinoblastoma. Arch Ophthalmol 1984;102:391–6.

20.Reese AB. Tumors of the eye. Hagerstown: Harper & Row, 1976, pp. 90–132.

21.Murphree AL, Villablanca JG, Deegan WF 3rd et al. Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Arch Ophthalmol 1996;114:1348–56.

22.Kingston JE, Hungerford JL, Madreperla SA, Plowman PN. Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol 1996;114:1339–43.

23.Shields CL, Honavar SG, Meadows AT. Chemoreduction for retinoblastoma: factors predictive of failure and need for treatment with external beam radiotherapy or enucleation. N Engl J Med 2003;(in press).

24.Scott IU, Murray TG, Toledano S, O’Brien JM. New retinoblastoma tumors in children undergoing systemic chemotherapy. Arch Ophthalmol 1998;12:1685–6.

25.Benz MS, Scott UI, Murray TG et al. Complications of systemic chemotherapy as treatment of retinoblastoma. Arch Ophthalmol 2000;118:577–8.

26.Howarth C, Meyer D, Hustu HO, Johnson WW, Shanks E, Pratt C. Stage-related combined modality treatment of retinoblastoma. Results of a prospective study. Cancer 1980;45:851–8.

27.Ajaiyeoba IA, Akang EE, Campbell OB, Olurin IO, Aghadiuno PU. Retinoblastomas in Ibadan: treatment and prognosis. West Afr J Med 1993;12:223–7.

28.Singh AD, Shields CL, Shields JA. Prognostic factors in retinoblastoma. J Pediatr Ophthalmol Strabismus 2000;37:1–8.

29.Gallie BL, Budning A, DeBoer G et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy.

Arch Ophthalmol 1996;114:1321–8.

30.White L. Chemotherapy for retinoblastoma: where do we go from here? Ophthalmic Pediatr Genet 1991;12:115–30.

31.Messmer EP, Heinrich T, Hopping W et al. Risk factors for metastases in patients with retinoblastoma. Ophthalmology 1991;98:136–41.

32.Magramm I, Abramson DH, Ellsworth RM. Optic nerve involvement in retinoblastoma. Ophthalmology 1989;96:217–22.

33.Shields CL, Shields JA, Baez KA et al. Choroidal invasion of retinoblastoma: Metastatic potential and clinical risk factors. Br J Ophthalmol 1993;77:544–8.

34.Shields CL, Shields JA, Baez KA et al. Optic nerve invasion in retinoblastoma. Cancer 1994;73:692–8.

35.Khelfaoui F, Validire P, Auperin A et al. Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution. Cancer 1996;77:1206–13.

36.Chantada GL, de Silva MTG, Fandino A et al. Retinoblastoma with low risk for extraocular relapse. Ophthalmic Genet 1999;20: 133–40.

37.Shields JA, Shields CL. Treatment of retinoblastoma with photocoagulation.Transac PA Acad Ophthalmol Otolaryngol

1990;42:951–4.

38.Shields JA, Shields CL. Treatment of retinoblastoma with cryotherapy.

Transac PA Acad Ophthalmol Otolaryngol 1990;42:977–80.

39.Abramson DH, Ellsworth RM, Rozakis GW. Cryotherapy for retinoblastoma. Arch Ophthalmol 1982;100:1253–6.

40.Shields CL, Santos MC, Diniz W et al. Thermotherapy for retinoblastoma. Arch Ophthalmol 1999;117:885–93.

41.Shields CL, Shields JA, Cater J et al. Plaque radiotherapy for retinoblastoma: Long term tumor control and treatment complications in 208 tumors. Ophthalmology 2001;108:2116–21.

42.Wolff JA, Boesel CP, Dyment PG et al. Treatment of retinoblastoma: a preliminary report. Int Congr Series (Amsterdam) 1981;570:364–8.

43.Zelter M, Damel A, Gonzalez G, Schwartz L. A prospective study on the treatment of retinoblastoma in 72 patients. Cancer 1991;68: 1685–90.

44.Mustafa MM, Jamshed A, Khafaga Y et al. Adjuvant chemotherapy with vincristine, doxorubicin, and cyclophosphamide in the treatment of postenucleation high risk retinoblastoma. J Pediatr Hematol Oncol 1999;21:364–9.

45.Hungerford J. Factors influencing metastasis in retinoblastoma. Br J Ophthalmol 1993;77:541.

46.Honavar SG, Singh AD, Shields CL et al. Post-enucleation adjuvant chemotherapy in high-risk retinoblastoma. Arch Ophthalmol 2002;120:923–31.

47.Uusitalo MS, van Quill KR, Scott IU et al. Evaluation of chemoprophylaxis in patients with unilateral retinoblastoma with high-risk features on histopathology examination. Arch Ophthalmol 2001;119:41–8.

48.Pratt CB, Crom DB, Howarth C. The use of chemotherapy in extraocular retinoblastoma. Med Pediatr Oncol 1985;13:330–3.

Background

Visual impairment is seldom life threatening. Nevertheless, it is among the most disabling of medical conditions and is more disabling than all chronic conditions except diabetes and cancer in older adults.1 Visual impairment is strongly associated with disability and dependency in daily activities,2–5 reduced physical activity,6,7 social isolation,8,9 and depression,10 especially in older individuals. According to one study,11 the quality of life of low-vision patients was significantly worse than that for age-matched controls and comparable to those with congestive heart failure or clinical depression.

Incidence and prevalence

The Royal National Institute for the Blind estimates that there are 1·7 million visually impaired individuals in the UK.12 Approximately 35 000 people are registered as blind or partially sighted per year, and as the number of registrations underestimates the true incidence by a factor of two to three, the actual number of incident cases may be as high as 100 000. Incidence and prevalence statistics depend on the definition of visual impairment. Most epidemiological studies use a definition based on restrictions in visual acuity, visual fields, or both. However, recent data2 suggest that other aspects of visual function, such as loss of contrast sensitivity or increased sensitivity to glare, independently contribute to visual disability. Were these other factors to be included in the definition of visual impairment then the numbers would be even greater.

Treatment options

Ninety per cent of visually impaired people are over 60 years of age13 with over half the incidence attributable to age-related macular degeneration (AMD). As there is no cure for this disease and currently available treatments merely retard the rate of vision loss, macular degeneration patients and many others with visually disabling eye conditions must learn to make best use of their residual vision. That is the goal of vision rehabilitation. Although it

has been estimated that over 150 000 low-vision consultations are offered annually in the UK at a cost of £21 million (plus the cost of low-vision aids) it is acknowledged that the availability of services is not adequate to meet the needs of the visually impaired population.12 In addition, it was the consensus of a panel of service providers and patients that vision rehabilitation services need to be more comprehensive.14 However, the evidence for the benefits of vision rehabilitation is limited. Surveys of patient satisfaction following vision rehabilitation have produced conflicting results ranging from 90% reporting that the service was sufficient to meet their needs15 to 50% reporting dissatisfaction.16 Similarly, there are wide discrepancies in the reported use of prescribed low-vision aids, such as magnifiers. Some studies find that 80–90% of patients find the devices useful for everyday activities,17,18 while others report that the majority of patients stop using the devices within 18 months.19 Without solid evidence as to the benefits of vision rehabilitation, it is difficult to argue for the expansion of rehabilitation services.

Question

What is the effectiveness of low-vision rehabilitation for visually impaired children or adults?

The evidence

We found no systematic reviews of randomised controlled trials of vision rehabilitation, although Cochrane reviews of low-vision devices and orientation and mobility training are currently underway. This review includes references from the Cochrance Eyes and Vision specialised register supplemented by an additional MEDLINE search. All controlled trials of visual rehabilitation were included, regardless of age of the participant, the type of intervention, location of the rehabilitation service (clinic or community), or cause of visual impairment. Studies that solely compared low-vision devices are not included.

We found eight randomised controlled trials, plus two trials that were controlled but not randomised. The ten studies are listed and summarised in Table 53.1. The total number of participants in the studies was 565. The smallest study

included only 17 participants and the largest 226. Age-related macular degeneration was the most common cause of visual impairment, but half of the studies did not specify the diagnosis. The type of intervention varied greatly among the studies. There were three studies of orientation and mobility (O&M) training, three studies of other types of training, three studies based on the provision of specific low-vision devices, and one comparison of a conventional hospital-based lowvision service to an expanded service with home visits by a rehabilitation officer. The interventions were too different from each other to be synthesised into a single meta-analysis.

The three O&M studies included similar small numbers of participants, 35–40. Only one of the studies20 showed a significant benefit of training. The trained group completed significantly more (86% v 82%) of the orientation, sighted guide, and independent travel activities correctly after 90 minutes per week for 10–12 weeks of O&M training. There was no significant change (61% v 60%) in the control group, who had a similar amount of physical exercise. One limitation of the study was that the preand post-training evaluations were carried out by O&M instructors who were not masked to the treatment assignment. Another concern was that the groups were not well matched for O&M skills prior to training. The other two studies20,21 that found no benefit of O&M training attributed their null findings to problems with the outcome measures. In one case20 the outcome was assessed by untrained volunteers whose assessments were not reliable. In the second case21 it was argued that the outcome measures (walking speed and travel errors) were too narrowly defined to capture the benefits of O&M training.

The three other training studies all reported significant benefits for their respective interventions. In a study of 40 patients with AMD,22 educational training in the use of lowvision aids that concentrated on eccentric viewing training improved patients’ ability to do near, intermediate, and distance tasks, compared to an untrained group. For example, prior to training none of the patients were able to read newspaper text. With low-vision aids 100% of the trained group, but only 25% of the untrained group were able to read newsprint. Another study of AMD patients10 evaluated the potential benefits of a self management training programme. Ninety-two patients were assigned to either six group sessions of behavioural skill training or no training. The trained group showed a significant improvement in mood and self-efficacy, compared to controls, but there was no difference on a generic quality of life scale. At the other end of the age spectrum, a study of 16 visually impaired children23 found that dance instruction plus physical education improved the children’s self concept of body position more than physical education alone. However, the two groups were not matched prior to the study. The dance instruction group had significantly worse position sense before training.

Three small studies of specific types of low-vision devices all reported a treatment benefit. One was a study of Fresnel prisms used to compensate for hemionopic visual field loss or visual neglect following stroke.24 Forty patients were randomly assigned to prism or no prism. Patients who received prism showed greater improvement in visual perception tests at the four-week follow up than the control group. However, there was no difference between groups in activities of daily living or mobility function. Prisms were also used in a study of 30 patients with AMD to enhance the use of eccentric vision.25 Visual acuity and self-reported function were assessed, although the methods used for the outcome assessment are not described. There was a trend towards more improvement in the prism group, but the results fell just short of statistical significance (P = 0·06). In the third study of low-vision devices, bioptic telescopes were prescribed to 17 low-vision patients with central vision loss caused by a variety of disorders. Half of the participants received O&M and driving training and half received no training. Outcomes were assessed for a wide variety of psychophysical tasks (such as peripheral letter recognition), functional tasks (such as visual memory), and driving simulator and on-the-road driving performance. The trained group showed significantly more improvement than the control group for half of the outcomes. There were no differences between groups for the remaining outcomes.

The largest and most thorough RCT of vision rehabilitation is a recent study of enhanced versus conventional low-vision services.26 Two hundred and twenty-six patients with AMD were randomly assigned to one of three groups: conventional hospital-based vision rehabilitation, the conventional service plus three home visits by a trained rehabilitation officer, or the conventional service plus home visits by a volunteer community care worker. The third group was included as a control for the additional social contact by the rehabilitation officer. There was a wide range of outcome measures including generic and vision-specific quality of life, psychological adjustment and activity restriction questionnaires, measured performance on several reading tasks, and an assessment of low-vision device usage. Contrary to expectations, there were no benefits observed for the enhanced intervention group on any of the outcome measures.

Discussion

Despite the substantial number of people with visual impairment there have been only a few, mostly small, controlled trials of vision rehabilitation. Seven of the 10 studies reviewed here reported statistically significant benefit from the intervention, and one reported a marginal benefit. The studies used a wide variety of outcome

Reported benefit for all

?

Yes

No

Yes

17 (C)

skills

60age

28 1991

Significant benefit

No

Yes

Significant benefit for

?

Yes

Group selfNo training Mood, self44 (I)

AMD

.,al etBrody

?

No?

and trainingno drivingincluding (C)8

age 16–78 years and training

27 2000

Yes No benefit of O&M

No

speedWalking (I),19

trainingO&M trainingNo

ageVarious,

.,al etSoong

and errors 18 (C)

years33–87

21 2001

Yes No benefit

Yes

measures ranging from performance-based assessments to generic quality of life questionnaires. The statistical treatment of the outcomes also varied from one study to the next. None of the investigations reported relative risks comparing intervention with control. Given the heterogeneity of interventions and outcomes it is not possible to pool the results from multiple studies.

There are many additional studies of the effectiveness of vision rehabilitation that did not include a control group. These have not been included in this review. Two of the included studies did not use random assignment to treatment and control groups, but because the groups were matched for important covariates they have been incorporated. In the Soong et al. O&M study21 the intervention group was recruited from an agency that provides O&M training while the control group was recruited from a university rehabilitation centre. The two groups were matched for age and level of impairment. Szlyk et al.’s study of bioptic telescope training27 used intervention and control groups that were matched for age and visual function but were not randomly assigned.

Several of the studies did not control for placebo effects in the form of additional social contract for low-vision patients in the treatment group. The Straw and Harley20 O&M studies and Straw et al.28 and the Russell et al. study of enhanced lowvision services26 are exceptions: Straw’s control groups participated in physical exercise and Russell included a control group with visits by a volunteer community care worker.

Only two of the 10 studies appeared to use masked examiners. In the remaining eight studies those who administered the outcome assessment could have been aware of whether the participant was assigned to the treatment or control group.

Four of the reviewed trials used patients with AMD and two additional studies were limited to older participants, many of whom had some form of macular disease. While AMD accounts for half of those referred for vision rehabilitation services in the UK and North America29,30 there is almost no evidence of the effectiveness of vision rehabilitation for children or adults of working age.

There have been no studies that compared conventional vision rehabilitation to no treatment. Given the widespread presumption that vision rehabilitation is beneficial, practitioners would be reticent to participate in a trial where their patients could be randomised to no treatment, and there are serious ethical concerns about designing such a study.

Implications for practice and research

Overall, the evidence of the effectiveness of vision rehabilitation is not strong. Larger trials are required and the diverse causes of visual impairment need to be considered.

More attention needs to be paid to the specification and statistical treatment of outcomes and the interpretation of potential benefits in terms of their impact on daily life.

References

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9.Thompson JR, Gibson JM, Jagger C. The association between visual impairment and mortality in elderly people. Age Ageing 1989;18: 83–8.

10.Brody BL, Williams RA, Thomas RG, Kaplan RM, Chu RM, Brown SI. Age-related macular degeneration: a randomized clinical trial of a selfmanagement intervention. Ann Behav Med 1999;21:322–9.

11.Scott IU, Smiddy WE, Schiffman J, Feuer WJ, Pappas CJ. Quality of life of low-vision patients and the impact of low-vision services. Am J Ophthalmol 1999;128:54–62.

12.Ryan B, Culham L. FRAGMENTED VISION – Survey of low vision services in the UK. London: Royal National Institute for the Blind, 1999.

13.Evans J. Causes of blindness and partial sight in England & Wales 1990–1991. Studies on Medical and population subjects: No. 57. London: HMSO, 1995.

14.Low Vision Consensus Group. Low vision services: Recommendations for future service delivery in the UK. London: Royal National Institute for the Blind, 1999.

15.Shuttleworth GN, Dunlop A, Collins JK, James CR. How effective is an integrated approach to low vision rehabilitation? Two year follow up results from south Devon. Br J Ophthalmol 1995;79:719–23.

16.McIlwaine GG, Bell JA, Dutton GN. Low vision aids – is our service cost effective? Eye 1991;5:607–11.

17.Leat SJ, Fryer A, Rumney NJ. Outcome of low vision aid provision: the effectiveness of a low vision clinic. Optom Vis Sci 1994;71: 199–206.

18.D’Allura T, McInerney R, Horowitz A. An evaluation of low vision services. J Vis Impair Blindness 1995;89:487–493.

19.Humphry RC, Thompson GM. Low vision aids – evaluation in a general eye department. Trans Ophthalmol Soc UK 1986;105: 296–303.

20.Straw LB, Harley RK. Assessments and training in orientation and mobility for older persons: Program development and testing. J Vis Impair Blindness 1991;85:291–6.

21.Soong GP, Lovie-Kitchin J, Brown B. Does mobility performance of visually impaired adults improve immediately after orientation and mobility training? Optom Vis Sci 2001;78:657–66.