Education and debate

Recent Advances: Ophthalmology

^a Forest Healthcare, Whipps Cross Hospital, London E11 1NR, ^b Institute of Ophthalmology and Moorfields Eye Hospital, London EC1V 2PD

Correspondence to: Mr Towler.

Advances or major changes in clinical practice can occur as a result of increased understanding of a pathological process or because of a technological advance that is then used in patient management. We concentrate on some of the recent advances or changes in management of common ophthalmic problems, some of which have become widely used without necessarily being subjected to rigorous clinical trials or knowledge of the long term sequelae.

Cataract surgery

Although phacoemulsification (ultrasound fragmentation of the lens) was pioneered in 1967 by Charles Kelman,¹ its widespread adoption as the preferred method of removing cataracts had to wait until ocular surgical techniques and intraocular lens technology caught up. Progress in cataract surgery has resulted from the combination of small, self sealing, sutureless wounds, the development of foldable intraocular lens implants, continuous curvilinear capsulorhexis (controlled circular tearing of the anterior lens capsule),² and improved techniques of phacoemulsification within the lens capsular bag. The impact of these advances has been to substantially reduce the period of visual rehabilitation after successful surgery to about one week and to rapidly accelerate the attainment of optimum visual acuity.

Cataract surgery is ideally suited to day case surgery under local anaesthetic, and most ophthalmic units now pursue this approach, often treating 90% of cases in this manner. Small incision phacoemulsification can even be performed under topical anaesthesia alone, further reducing the morbidity of intervention. Improved design of wound construction has allowed self sealing of wounds, thereby avoiding the need for sutures, which virtually abolishes surgically induced astigmatism and eliminates the need for subsequent removal of sutures. Foldable lenses made from various materials (usually silicone) can be inserted through an astigmatically neutral 3.2 mm incision, whereas rigid intraocular lens implants are manufactured from polymethylmethacrylate (PMMA) and require an incision of 5 mm or more in the sclera or cornea for introduction. The newer lens materials may have other advantages, such as a lower incidence of cell deposits on the lens surface and a lesser degree of capsular fibrosis and opacification. Small surgical incisions produce little distortion of the cornea and are less likely to leak or rupture if the cornea is traumatised.

The main disadvantage of cataract surgery by small incision phacoemulsification is the steep learning curve with its attendant rate of complications. The most notable complication is the "dropped nucleus," in which the lens nucleus or fragments fall through a tear in the posterior lens capsule into the vitreous cavity; these have to be removed by vitrectomy, often by means of perfluorocarbon "heavy" liquids to float the nucleus up into the anterior chamber, from where it can be safely removed. Small incision phacoemulsification undoubtedly has higher intraoperative consumable costs than "conventional" extracapsular methods, but these are considerably offset by the reduced number of postoperative follow up visits required and the high level of patient satisfaction.

Photorefractive keratectomy

The cornea accounts for two thirds of the refractive power of the eye and can be reshaped by several surgical methods. Photorefractive keratectomy is a technique of modifying the refractive power of the cornea by laser ablation of the central area, thereby rendering the eye less short sighted.³ Trials of excimer laser photorefractive keratectomy for myopia started in 1989 in Germany and Britain, and later in the United States. Since then photorefractive keratectomy has been widely heralded as the cure for myopia, but it is not without substantial side effects and not all patients respond to treatment in a predictable manner. Patients who are slightly shortsighted (below -3.00 D) do well, with a 12% incidence of undercorrection of greater than 1.00 D, but those with severe myopia (greater than -6.00 D) have a 60% incidence of under-correction. In addition, about 20% of patients lose one or more lines of Snellen vision after the procedure, and again this risk is greater for patients with more severe myopia. Other common side effects include haloes around lights, diminished night vision, and ocular tenderness.

Demand for photorefractive keratectomy is consumer led, and, since slight myopia is not a disease but essentially a cosmetic hindrance, it is extremely important that patients are given a realistic appraisal of the benefits and disadvantages of the technique before they consider embarking on this new treatment.

Botulinum toxin

Injection of botulinum toxin was first reported to be of value in managing strabismus in 1981, and since then the indications for its use in specific clinical situations have become more clearly defined. The toxin is injected directly into the chosen muscle under electromyographic control, a quick procedure that can be performed on an outpatient basis with minimal risk of systemic effects. The toxin produces a transient neuromuscular paralysis that usually starts 12-24 hours after injection, reaches maximal paralysis by 10 days, and lasts for two to three months.

The ocular indications for injection of botulinum toxin include certain types of strabismus,^{4 5} essential blepharospasm, and induction of ptosis to protect the cornea. More recently, its use in nystagmus has also been described. In patients with acquired nystagmus causing debilitating symptoms such as oscillopsia, retrobulbar injection of toxin was associated with subjective and objective improvement and reduction in the amplitude but not the frequency of the nystagmus.⁶ Latent nystagmus (nystagmus that is only apparent or is considerably worse when one or other eye is covered) is not usually symptomatic, but when it is, injection of toxin into the medial rectus allows accurate assessment of the visual potential of the beating eye and may stabilise the nystagmus since latent nystagmus is often dampened in adduction.⁷

Disposable contact lenses

These were introduced in the late 1980s, predominantly for slight and moderate myopia, and were originally intended to be worn continuously for one to two weeks. They have become widely used, largely because they provide freedom from daily handling and maintenance of the lenses. However, continuous wearing of disposable lenses, or even wearing only during the day, can lead to serious complications, the most serious being corneal infection.

In the past two years disposable, single use lenses have become available at a cost not very different from that associated with wearing conventional soft contact lenses. Preliminary studies of these lenses in the United States have indicated high acceptability to users and low rates of complications.⁸ For people who can be fitted with a standard size, these lenses should be relatively trouble free, although a case of ulcerative keratitis has been reported.⁹ The risk of corneal infection will become a problem only if the instructions for the use of the lenses are not followed, as they do not come packed in sterilising solutions and should not be repeatedly handled.

More power ranges (for example, for hypermetropia, bifocal, and toric designs) will probably become available over the next few years, increasing the potential number of wearers. The concept of disposable contact lenses is not new--they have been used for some years as bandage lenses when medically indicated for problems with the ocular surface.¹⁰

Age related macular degeneration

Patients with age related macular degeneration who have subretinal choroidal neovascularisation (figs 1 and 2) generally have a poor visual prognosis.¹¹ Recently, several new treatments have been introduced, including foveal ablation by laser photocoagulation,¹² supplementation of dietary zinc,¹³ interferon alfa,¹⁴ radiotherapy,¹⁵ and subretinal surgery.¹⁶

View larger version (124K): [in this window] [in a new window]   Fig 1--Fundus photograph of subfoveal and extrafoveal choroidal neovascularisation in age related macular degeneration

View larger version (111K): [in this window] [in a new window]   Fig 2--Fluorescein angiogram showing dye leakage (two dense white areas) corresponding to choroidal neovascular membranes

Laser photocoagulation--The use of laser to treat subfoveal choroidal neovascularisation may reduce the eventual size of the central scotoma.¹² However, it is associated with an immediate drop in Snellen acuity of about three lines, which may be difficult for a patient to accept in the better eye since the condition is often bilateral.

Dietary zinc supplements were given in the hope that zinc dependent enzymatic pathways in the retinal pigment epithelium would be enhanced and increase the removal of phagocytosed photoreceptor debris. However, the initial optimism was not realised by long term clinical trials.

Interferon alfa administered by subcutaneous injection was initially reported to be helpful,¹⁴ but a recent trial did not find any important benefit (A C Bird, personal communication).

Radiotherapy--A pilot study of low dose radiotherapy to the macular region in patients with expanding subfoveal choroidal neovascularisation has recently reported encouraging results. Experimental studies had shown that neovascular complexes in healing ocular wounds were significantly inhibited by doses of (gamma) radiation greater than 9.5 Gy.¹⁷ Since the risk of radiation retinopathy is low if eyes are exposed to less than 25 Gy, a dose of 10-15 Gy of 6 MV photons was selected and applied to the posterior pole of the eye. At six and 12 months after treatment, 78% and 63% respectively of treated patients had maintained or improved their visual acuity with reduction in size of the choroidal neovascularisation, whereas visual acuity had slowly deteriorated in the untreated control patients. A multicentre trial is now in progress to further assess this treatment.

Surgery--Surgery for age related macular degeneration has proved to be of little value in enhancing visual recovery, although individual patients may benefit by stabilisation of visual acuity, lessening of distortion, and reduction in size of scotomas. The two main techniques used are surgical removal of subfoveal choroidal neovascularisation through a small retinal incision¹⁷ and transplantation of retinal pigment epithelium cells.¹⁸ Surgical removal of neovascularisation has proved more successful in improving vision in younger patients with choroidal neovascularisation secondary to inflammatory disorders affecting the choroid than in age related macular degeneration, where there is often considerable damage to photo-receptors and the retinal pigment epithelium. Cultured cells of fetal retinal pigment epithelium have been transplanted as a monolayer patch into the subretinal space, but so far this has achieved only a modest and transient improvement in visual function. Since atrophic age related macular degeneration is an increasingly common problem with enhanced longevity, transplantation may offer the greater promise in overcoming this major cause of blindness.

Inherited retinal dystrophies

These disorders are genetically determined and differ from each other in their mode of inheritance, pattern of visual loss, and clinical appearance on ophthalmoscopy. They can be divided into broad groups depending on their clinical features, and the largest number fall into the category of retinitis pigmentosa (fig 3). Many mutations have been detected in the rhodopsin gene,¹⁹ and this gene seems to account for about 30% of cases of autosomal dominant retinitis pigmentosa. Most mutations seem to be specific to a particular family, but some have been found in different parts of the world, which may still reflect a large pedigree. Abnormalities in other genes have also been implicated in retinitis pigmentosa, including one in the gene for peripherin,²⁰ a glycoprotein thought to be essential for normal outer segment discs of the retinal photoreceptors. Mutations in the gene coding for the ß subunit of phosphodiesterase have been recorded in patients with autosomal recessive retinitis pigmentosa.²¹

View larger version (123K): [in this window] [in a new window]   Fig 3--Fundus photograph showing typical pigmentary disturbance in peripheral retina in retinitis pigmentosa

Although such genetic findings have not yet provided a treatment for these diseases, counselling of patients and relatives is much more accurate if the genomic abnormality is known. The distribution of the abnormal gene can be mapped in a family, and the genetic status of an individual can be identified at any stage of the disease, which is otherwise not always possible and which is particularly important in X linked diseases.

Intraocular slow release drug devices

Cytomegalovirus is the commonest cause of retinitis in patients with AIDS, and once it has occurred lifelong antiviral treatment is necessary as current drugs are virustatic rather than virucidal. Ganciclovir is the most commonly used drug and can be given systemically (in which case it can cause many side effects) or by injection into the vitreous cavity of the eye. Intraocular injections need to be repeated frequently to control the disease, but this can now be avoided by implanting a device inside the eye that slowly releases ganciclovir for up to nine months.^{22 23} When it is exhausted the implant can be replaced with another, and only low rates of infection and retinal detachment have been reported.²⁴ The implant, however, gives no protection to the second eye, so patients need careful monitoring, with the addition of systemic treatment when necessary.

Macular hole surgery

The unique anatomical structure of the fovea predisposes to the development of localised retinal holes at the macula (fig 4), most commonly in women in their 70s. This leads to impaired visual acuity, which is often made worse by the presence of a cuff of subretinal fluid around the hole. Until recently, these full thickness macular holes were considered essentially untreatable, and attention was devoted to treating impending macular holes by vitrectomy in the hope of preventing or minimising loss of central vision. Unfortunately, randomised controlled studies have failed to show any significant benefit of surgery for impending holes.²⁵

View larger version (110K): [in this window] [in a new window]   Fig 4--Fundus photograph showing full thickness macular hole with surrounding cuff of subretinal fluid

However, vitrectomy combined with intraocular gas tamponade, particularly with long acting gases such as perfluoropropane (C3F8), can successfully close established age related or traumatic macular holes and result in significant visual improvement. Glaser and coworkers have pioneered the use of recombinant transforming growth factor-ß to enhance closure of the hole,²⁶ but autologous serum,²⁷ plasma,²⁸ and platelet rich plasma may be equally effective and considerably less expensive. Patient selection is important for two reasons: long standing holes (>6 months' duration) do not do well, and a face down posture is crucial during the postoperative period--usually for several weeks--until the gas bubble is reabsorbed. Vitrectomy with gas tamponade has complications: one recent series recorded a 14% incidence of retinal detachment from peripheral retinal breaks--a rate of about 5% might normally be expected--and an increased risk of cataract development from the long acting intraocular gases.²⁹

The ability to separate the posterior vitreous face from the retina and create an iatrogenic posterior vitreous detachment in other clinical situations has aroused considerable interest. The spontaneous development of a posterior vitreous detachment may be associated with the development of retinal holes at the macula or, more commonly, in the more peripheral retina, which can lead to rhegmatogenous retinal detachment. Retinal neovascularisation (for example, in proliferative diabetic retinopathy or after retinal vein occlusion) requires the presence of an attached vitreous gel as a scaffold for the new vessels and is virtually abolished in the presence of a posterior vitreous detachment. Intravitreal injection of an expanding gas has been used to create a posterior vitreous detachment with subsequent closure of 13 out of 17 early macular holes and without important side effects.³⁰ Although no retinal detachments occurred in this small series, it is unlikely that the technique will be completely free from this serious complication.

We thank Mr Roger J Buckley and Professor Alan C Bird for their help in the preparation of this article.

1. Kelman C. Phacoemulsification and aspiration. A new technique for cataract removal. A preliminary report. Am J Ophthalmol 1967;64:23-35. [Medline]
2. Neuhann T. Theorie und Operationstechnik der Kapsulorhexis. Klin Monatsbl Augeneilkd 1987;190:542-5.
3. Gartry DS. Treating myopia with the excimer laser: the present position. BMJ 1995;310:979-85. [Abstract/Free Full Text]
4. Murray A. Strabismus: challenges and trends. Eye 1993;7:332-40.
5. Scott A, Magoon E, McNeer K, Stager D. Botulinum treatment of childhood strabismus. Ophthalmology 1990;97:134-8.
6. Repka M, Savino P, Reinecke R. Treatment of acquired nystagmus with botulinum neurotoxin A. Arch Ophthalmol 1994;112:1320-4. [Abstract]
7. Liu C, Gresty M, Lee J. Management of symptomatic latent nystagmus. Eye 1993;7:550-3.
8. Nason RJ, Boshnick EL, Cannon WM, Dubow BW, Freeman MI, Kame RT, et al. Multisite comparison of contact lens modalities. Daily disposable wear versus conventional daily wear in successful contact lens wearers. J Am Optom Assoc 1994;65:774-80. [Medline]
9. Hingorani M, Buckley R. Ulcerative keratitis in a daily disposable contact lens wearer. Br J Ophthalmol 1995;79:1138.
10. Rubinstein M. Disposable contact lenses as therapeutic devices. Journal of the British Contact Lens Association 1995;18:95-7.
11. Bressler S, Bressler N, Fine S, Hillis A, Murphy R, Olk J, Patz A. Natural course of choroidal neovascular membranes within the foveal avascular zone in senile macular degeneration. Am J Ophthalmol 1982;93:157-63. [Medline]
12. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Arch Ophthalmol 1991;109:1220-31. [Abstract]
13. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E. Oral zinc in macular degeneration. Arch Ophthalmol 1988;106:192-8. [Abstract]
14. Fung W. Interferon alpha 2a for treatment of age-related macular degeneration. Am J Ophthalmol 1991;112:349-50. [Medline]
15. Chakravarthy U, Houston R, Archer D. Treatment of age-related sub-foveal neovascular membranes by teletherapy: a pilot study. Br J Ophthalmol 1993;77:265-73. [Abstract/Free Full Text]
16. Lambert F, Capone A, Aaberg T, Sterberg P, Mandell B, Lopez P. Surgical excision of subfoveal neovascular membranes in age-related macular degeneration. Am J Ophthalmol 1992;113:257-62. [Medline]
17. Chakravarthy U, Gardiner T, Archer D, Maguire C. A light microscopic and autoradiographic study of non-irradiated and irradiated ocular wounds. Curr Eye Res 1989;8:337-48. [Medline]
18. Algvere PV, Berglin L, Gouras P, Sheng Y. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol 1994;232:707-16. [Medline]
19. Bird A. Retinal photoreceptor dystrophies. Am J Ophthalmol 1995;119:543-62. [Medline]
20. Wrobleski J, Wells J, Eckstein A, Fitzke F, Jubb C, Keen T, et al. Ocular findings associated with a three-base pair deletion in the peripherin-RDS gene in autosomal dominant retinitis pigmentosa. Br J Ophthalmol 1994;78:831-6. [Abstract/Free Full Text]
21. McClaughlin M, Sandberg M, Berson E, Dryja T. Recessive mutations in the gene encoding the beta-subunit of phosphodiesterase in patients with retinitis pigmentosa. Nature Genetics 1993;4:130-4. [Medline]
22. Sanborn GE, Anand R, Torti RE, Nightingale SD, Cal SX, Yates B, et al. Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Use of an intravitreal device. Arch Ophthalmol 1992;110:188-95. [Abstract]
23. Martin DF, Parks DJ, Mellow SD, Ferris FL, Walton RC, Remaley NA, et al. Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. A randomized controlled clinical trial. Arch Ophthalmol 1994;112:1531-9. [Abstract]
24. Morley M, Duker J, Ashton P, Robinson M. Replacing ganciclovir implants. Ophthalmology 1995;102:388-92. [Medline]
25. De Butros S, for the Vitrectomy for Prevention of Macular Hole Study Group. Vitrectomy for the prevention of macular holes. Results of a randomized multicenter clinical trial. Ophthalmology 1994;101:1055-60. [Medline]
26. Glaser BM, Michels RG, Kupperman BD, Sjaarda RN, Pena RA. Transforming growth factor-beta 2 for the treatment of full-thickness macular holes. A prospective randomised study. Ophthalmology 1992;99:1162-72. [Medline]
27. Christmas NJ, Skolik SA, Howard MA, Saito Y, Barnstaple CJ, Liggett PE. Treatment of retinal breaks with autologous serum in an experimental model. Ophthalmology 1995;102:263-71. [Medline]
28. Blumenkranz MS, Coll GE, Chang S, Morse LS. Use of autologous plasma-thrombin mixture as adjuvant therapy for macular hole. Ophthalmology 1994;101(suppl):69.
29. Park SS, Marcus DM, Duker JS, Pesavento RD, Topping TM, Frederick AR, et al. Posterior segment complications after vitrectomy for macular hole. Ophthalmology 1995;102:775-81. [Medline]
30. Chan CK, Wessels IF, Friedrichsen EJ. Treatment of idiopathic macular holes by induced posterior vitreous detachment. Ophthalmology 1995;102:757-67. [Medline]