- Email: [email protected]
What’s new in ophthalmic surgery
What’s New in Ophthalmic Surgery Norman Shorr, MD, FACS, Robert Alan Goldberg, MD, FACS, Todd Cook, MD
“What’s New in Surgery” evolves from the contributions of leaders in each of the fields of surgery. In every instance the author has been designated by the appropriate Council from the American College of Surgeons’ Advisory Councils for the Surgical Specialties. This feature is now presented in issues of the Journal throughout the year.
Ophthalmology as a field is characterized by subspecialization. Comprehensive ophthalmologists (“generalists” who do not focus their practice in an ophthalmic subspecialty) continue to represent the majority of practicing ophthalmologists, and their practice typically includes cataract, external ocular disease, including infections and inflammations, glaucoma, and refractive disorders. Advanced medical and surgical problems are typically referred to ophthalmic subspecialists. Nationally, one-fourth of graduating ophthalmology residents go on to fellowship training, and at academic programs, it is not unusual for the majority of the graduating class to pursue subspecialty fellowship training. Especially in urban areas, ophthalmic subspecialists often limit their practice to their subspecialty and do not take care of general problems such as cataract. Currently, organized ophthalmic fellowship training is available in orbitofacial and ophthalmic plastic surgery, retina, cornea and refractive surgery, glaucoma, neurophthalmology, ophthalmic pathology, and pediatric and adult strabismus. Even within the ophthalmic subspecialties, there is a tendency for further specialization. For example, some cornea fellowships, and cornea specialists, focus exclusively on refractive surgery. Orbitofacial and ophthalmic plastic surgery is a broad discipline and there has been a tendency toward additional specialization in aesthetic surgery, lacrimal surgery, and orbital surgery. This update will follow the pattern of subspecialization and focus on developments in the various subspecialties that have most significantly affected patient care, or that have
the greatest potential to affect the care of patients in the future. The political arena: Optometrists seek medical and surgical privileges
One area that has significantly affected ophthalmology in recent years has been ongoing discussion in the political arena regarding the appropriate role of our professional colleagues in optometry. Optometrists are nonphysicians who train in a 3-year program after college. Traditionally, optometrists focused their practice on nonmedical eye screening and refraction (glasses and contact lenses). Some ophthalmologists employ optometrists in their practice to help with patient screening and refraction. As a profession, optometrists seek increasing privileges in patient care, and through well-orchestrated political activities, they have achieved by legislation the ability in most states to independently prescribe oral and topical medications including steroids, antibiotics, antivirals, and narcotics. The training requirements, for example, 6-week pharmacology courses, and oversight for quality of prescribing and practice, are overseen by a board of optometry, independent from the medical board. Optometrists do not complete medical school, medical or surgical internship, or residency training, and at the current time they do not have privileges to perform operations, although there is movement in that direction; for example, in some states optometrists have lobbied for privileges to perform laser surgery. Ophthalmology organizations have taken the position that it requires medical training to best diagnose ophthalmic disease (which is inseparable from systemic disease), to most safely and effectively prescribe medications and perform operations, and to anticipate and recognize potential side effects and complications. The focus of political lobbying has been to emphasize that there is, in
Received July 24, 2001; accepted July 24, 2001. From the Jules Stein Eye Institute, Department of Ophthalmology, UCLA Medical Center, Los Angeles, CA. Correspondence address: Norman Shorr, MD, FACS, 435 N Roxbury Dr, Suite 104, Beverly Hills, CA 90210.
© 2001 by the American College of Surgeons Published by Elsevier Science Inc.
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fact, enormous value in the intense didactic, practical, and ethical training that is encompassed by medical school, internship, and residency training, and that the issue at hand is not primarily professional economic rivalry, but protection of the public. Orbitofacial and ophthalmic plastic surgery: Enlarging in a time of contraction
Oculoplastic surgery is a relatively young subspecialty. In the 1960s, some ophthalmologists sat around a restaurant table discussing the value of forming an organized subspecialty group of ophthalmologists who were interested in plastic surgery around the eye. Early on, the field of oculoplastics was small both in terms of numbers (there were just a handful of fellowships) and scope. Fellowships were 6 months. It was rare to find oculoplastic surgeons who limited their practice to oculoplastics. For the most part, oculoplastic surgeons focused on a limited number of surgical procedures and problems, and there was not much interest in extending outside the orbit complex. The field has exploded since that time and is evolving into a broader discipline that, echoing the discipline of maxillofacial surgery, might best be called orbitofacial surgery. There are now more than 400 members of ASOPRS (the American Society of Ophthalmic Plastic and Reconstructive Surgery) and fellowships are 2 years long, with many fellows taking additional subsubspecialty training after 2 years of fellowship. The result of this massive influx of intellectual talent has been a blossoming of research and education that has enormously expanded our knowledge of anatomy and function of the orbit, eyelid, and face. Starting from the nucleus of the eye, arguably the most important functional and esthetic structure of the face, orbitofacial fellowship programs now take advantage of increased time and increased knowledge to train fellows in a wide range of anatomic and surgical principles involving the extended orbital bony complex and the extended eyelid complex, including the eyebrow and midface. A small group of oculoplastic surgeons have been doing facelifts for many years (for example, in the 1997 Wendell Hughes lecture at the American Academy of Ophthalmology, Henry Baylis summarized a 15-year experience) and increasing numbers of ASOPRS-approved fellowships are offering or plan to offer facelift training as part of the fellowship curriculum. Ophthalmology-trained orbitofacial surgeons have a
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great deal to contribute to the field of esthetic and reconstructive facial surgery. The extended eyelid complex, including the eyebrow and forehead superiorly and midface inferiorly, is the focal point of the entire face, both functionally and esthetically. Attention to and correction of the midface and lower eyelid contour has replaced the now outdated ideas of blepharoplasty to remove excess skin, muscle, and fat.1 Rather than tightening laterally through a preauricular incision, the midface, which descends inferiorly, is more appropriately elevated superiorly. It is best addressed in conjunction with, and typically through, the same incision as the lower eyelid rejuvenation. So midface lifting, which is the single most important aspect of midface and facelift contouring, falls directly into the responsibility of the eyelid surgeon.2 Excellent thinkers from many disciplines have helped define the anatomy and function of these anatomic structures, but certainly some of the pivotal and innovative contributions have come from ophthalmology. An example of the unique anatomic and philosophic perspective that ophthalmic-trained orbitofacial surgeons bring to facial surgery is the anatomic description of the midfacial orbital ligaments and depressor supracilli muscle by Lucarelli and colleagues.3 Orbital facial esthetic surgery focuses increasingly on small incision and nonincisional techniques. No group is more conservative or reverent to eyelid function than ophthalmologists, who for years have had to manage some of the worst complications of traditional blepharoplasty techniques. Older techniques of blepharoplasty that focused on excision of skin, muscle, and fat were destructive not only to eyelid function, sometimes with disastrous results, but also to the esthetic beauty of the eyelid complex. Look in any celebrity magazine for examples of surgical-appearing eyelids, with hollowappearing orbit and change in shape of the eyelid aperture. Newer concepts of fat preservation,4 fat repositioning,5 conservative sculpture, minimal skin and muscle removal,1 and small-incision surgery for the forehead6 and midface have contributed to the field of esthetic facial surgery not only in reduced functional complications, but also in improved, more natural esthetic results. Ophthalmologists introduced botulinum toxin to the medical community in the 1980s as a treatment for strabismus and blepharospasm. Oculoplastic surgeons began using botulinum toxin for esthetic purposes in the early 1990s. Botulinum toxin treatment for wrinkles,
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facial asymmetry, frown lines, and undesired dynamic irregularities is now extremely popular, and practiced by physicians from a number of disciplines including plastic surgery, facial plastic surgery, and dermatology. It is probably the single most important advance in esthetic facial surgery of the last decade because it offers a noninvasive technique to address concerns that previously would have been treated surgically, often with less predictable and certainly less reversible results. Facial anatomy and surgical techniques are covered in the ophthalmology residency, and increasing numbers of programs offer significant exposure to esthetic surgery during the residency, but in reality most ophthalmology residents, just like residents coming from other specialties, will want to take additional training in esthetic surgery to feel confident in this rapidly expanding discipline. This training will typically involve 2 years of oculoplastic fellowship and then often additional training in esthetic reconstructive orbitofacial surgery. Ophthalmic-trained orbitofacial surgeons are not the only subspecialists with expertise in esthetic and reconstructive surgery of the face. As physicians from many training backgrounds enter the field of esthetic surgery, the public is best protected by establishing crossdisciplinary standards for board certification and board equivalency. Currently the issue of credentialing for esthetic facial surgery is in evolution. A physician and surgeon’s license entitles one to operate on the face from a legal standpoint. Hospital staffs control what is done by various specialties in the hospital operating rooms, but there is currently little state and no federal regulation of procedures done in an office setting. Although the American Society of Ophthalmic Plastic and Reconstructive Surgery requires for Fellowship a written and oral examination and completion of an approved postresidency training program, ophthalmic plastic surgery is not recognized as a specialty by the American Board of Medical Specialties. A number of ophthalmology-trained orbitofacial surgeons have now successfully sat for the American Board of Cosmetic Surgery, a crossdisciplinary credentialing organization. Like all disciplines that incorporate plastic and reconstructive surgery, ophthalmic plastic surgery meetings and journals are characterized by a preponderance of mechanical papers that discuss iterative adjustments to previous anatomic or surgical ideas; not infrequently, a careful review of the ancient medical literature (before
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1966, we mean) reveals that the idea was already thought of and forgotten. This is not to belittle those innovative surgeons who continue to try to refine our current anatomic and mechanical concepts. Rather, it reflects the fact that reconstructive surgery is straining at the bounds of its ability to get much better based on current technology. The great breakthroughs of the future will not be mechanical, but rather biological. It is our inability to control wound healing that most severely limits our results.7 New work in growth factors to increase the revascularization of orbital implants8 is an excellent example of the ability of this nascent technology to improve our ability to help patients with surgery. Often, the ability not to encourage but rather to discourage the body’s natural healing response is critical to successful surgical outcomes. One of the best examples of the successful application of biologic agents to attenuate unwanted wound healing response is the use of mitomycin-C. Mitomycin-C has been used by ophthalmologists to prevent closure of the fistula created on the eyeball to lower the pressure in glaucoma surgery. More recently, in the discipline of lacrimal surgery, mitomycin-C has been used to prevent closure of the newly created ostium in dacryocystorhinostomy. An increasing body of experimental and clinical data9,10 suggests that application of mitomycin-C solution, 0.4 mg per mL, to the newly created surgical opening successfully tipped the balance of biologic forces toward maintaining, rather than closing, the ostium. The surgical principle embodied by this work should be applicable to a number of surgical disciplines. Cornea and refractive surgery
The cornea is the body’s clear window to the world and is made up of many layers, each with different functions. Severe corneal epithelial disease results in blurred vision because of a loss of clear refracting media. Corneal epithelial cells are produced from stem cells that are located at the limbus (the junction of the white and clear areas of the eye). Once stem cells are lost the corneal epithelial cells are replaced by conjunctival epithelial cells, which do not provide clear refractive media. Limbal stem cell transplantation is a new technique offering hope of visual recovery to patients with severe corneal epithelial surface disease.11 Autografts are used in cases of severe unilateral disease or bilateral cases with relative sparing of one eye and have the advantage of not requiring immunosuppression. Allografts from living related do-
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nors12 or cadavers13 have also been used with limited success with immunosuppression. Refractive surgery involves manipulating the eye to overcome its inherent inability to focus light on the retina, ie, nearsightedness, farsightedness, and astigmatism. Keratorefractive surgery involves changing the shape of the cornea to overcome inherent refractive errors. Older techniques (RK, radial keratotomy) accomplished this by making incisions in the cornea to flatten or steepen it to achieve clear vision without the need for corrective lenses. More recently lasers have been used to ablate the cornea in predetermined areas to achieve the same effect. PRK (photorefractive keratotomy) accomplishes this by first scraping off the corneal epithelium and then applying laser ablation to the corneal stroma. Visual recovery takes days to weeks as the corneal epithelium heals over the ablated corneal stromal bed. LASIK (laser-assisted in situ keratomileusis) is like PRK in that a laser is used to ablate the corneal stroma, but instead of scraping off the corneal epithelium, a hinged flap of cornea is created with a keratome. Keratomes differ in design; some are manual and some are automatic. Some cut in a straight line and others cut while rotating on an axis. All share common features including a suction system that couples the eye to the keratome. Corneal flap creation is not without problems. Commonly reported complications include free flaps (caps), incomplete flaps, flap striae, ablation of flap hinges, epithelialization under flaps, microbial keratitis, and dry eyes.14-16 Once the flap is created it is displaced out of the laser field during the ablation and then replaced to its original position. Remarkably, after careful replacement and adequate drying (minutes) the corneal flap is stable and visual recovery is, in most cases, nearly instantaneous. Historically, accurate laser ablation of the corneal stroma required careful, steady patient ocular fixation in order to achieve predictable ablation. Poor postoperative results have been attributed to loss of or poor intraoperative visual fixation. Laser design and failure to calibrate the laser to compensate for temperature and humidity have also led to poor postoperative results. New technology attempts to overcome these problems. Gaze tracking systems now allow the laser to ablate cornea only when the patient is optimally fixated and even allow patients with nystagmus to undergo refractive surgery.17 Protocols now require more than daily calibration. Wave front technology may allow for custom corneal ablation in-
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stead of the current one size fits all approach, which may improve results to better than 20/20. Other techniques are also being used to overcome the inherent refractive error of the eye. Corneal stromal rings (Intacs) are another keratorefractive technique for changing the shape of the cornea.18 Thought to be reversible, this technique involves making a vertical, partial thickness incision into the cornea. A special keratome is used to create arcuate intrastromal tunnels into which clear polymethyl methacrylate, half ring-shaped implants are introduced. This technique is also fraught with potential complications including microbial keratitis and under- or overcorrections. Phakic intraocular lens implantation capitalizes on familiar techniques used in cataract surgery to introduce an artificial lens inside the phakic eye.19 Ironically, a cataract can result, requiring further surgical correction. Other potential devastating complications include endophthalmitis and glaucoma. Although most patients are able to improve their ability to read the eye chart after refractive surgery, many successfully treated patients suffer from other effects of the procedure that can be debilitating and irreversible, including loss of contrast sensitivity and nyctalopia. Careful preoperative evaluation of patients can avoid many potential surgical complications and identify those predisposed to difficulty with the effects of surgery. Cataract surgery
Successful cataract surgery involves removal of a cloudy lens and replacement with an artificial lens. Most procedures are done on an outpatient basis under local or topical anesthesia. Removal of the lens nucleus and cortex from within the lens capsule is accomplished with ultrasonic emulsification (phacoemulsification) and suction. Alternatives to ultrasonic emulsification are being developed, including laser ablation of the lens,20 but are currently not used in clinical practice in the United States. Intraocular lenses are positioned in the remaining capsular bag; there they remain static, uncoupled to the intrinsic focusing mechanism of the eye. Consequently, the eye focuses at one distance, predictable by careful preoperative measurements, and the patient is left wearing corrective lenses to see clearly at other distances. Another strategy for overcoming this is “monovision correction,” which involves correcting one eye for distance and one eye for near. This has been accepted with varying results. Recently, multifocal intraocular lenses
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have been developed and implanted, overcoming the near-distance discrepancy by having zones of differing focusing power in the lens. So a patient is able to see clearly at all distances without requiring additional lenses under most viewing conditions. The multifocal design is responsible for much of the disfavor with this form of correction. Lens-edge effect as well as zone-edge effect have led to difficulty with glare and contrast sensitivity in some patients.21 Other techniques for coupling an intraocular lens to the inherent focusing mechanism of the eye are currently being investigated but are not used in clinical practice. Retinal disease and surgery
Age-related macular degeneration (AMD) distorts and sometimes robs elderly patients of their central vision. This feared disease has until recently been a visual death sentence with permanent social and economic sequelae. AMD comes in two forms, both only affecting the anatomic spot responsible for central vision called the macula. The dry form, which is the most common, usually leads to slow distortion of central vision. Clinically it is identified by deposition of waste products in the layers underneath the retina called the retinal pigment epithelium and Bruch’s membrane. These two layers are to the eye what the liver is to the body. The wet form of AMD involves a break in the retinal pigment epithelium and Bruch’s membrane, allowing neovascular membranes to invade and distort the retina. The consequence of these membranes is central blindness. Unfortunately, laser coagulation of these membranes has been hampered by collateral damage (a permanent blind spot in the treatment area) and recurrence, usually in a worse anatomic position. Past enthusiasm has centered on antioxidant supplementation as an attempt to halt or slow the degeneration,22,23 potentially preventing the normal to dry to wet progression. Recently a new therapy combining laser technology with photosensitizing drugs has shown some benefit in treating wet AMD.23 Photodynamic therapy involves giving patients an intravenous photosensitizing drug (verteporfin) and then treating the eye with lowpowered laser over a long duration. This technique has been shown to selectively coagulate certain types of neovascular membranes with minimal collateral damage. The downside of this therapy has been modest visual improvement at best, and the need for multiple retreatments as often as every 3 months. The cost for each
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treatment is currently more than $1,000 just for the drug, and this will certainly become a larger issue in the years to come. Other new alternatives for patients who have already lost central vision from AMD are to physically move the retina to an overlying area of normal retinal pigment epithelium and Bruch’s membrane24 or to surgically remove the neovascular membrane.25 Macular translocation surgery accomplishes this by first cutting the retina, detaching it, and reattaching it to an area with healthy underlying tissue. Submacular surgery involves retinotomy, detachment of the retina, removal of the membrane, and reattachment of the retina. Visual results have varied and complications have been reported. A technique that may prove beneficial in the future is retinal pigment epithelial transplantation.26 Glaucoma
Glaucoma is a neuropathy of the optic nerve leading to loss of peripheral and later central vision with characteristic clinical changes in the optic nerve head. High intraocular pressure has historically been synonymous with glaucoma. But other forms of glaucoma not associated with high intraocular pressure have been identified, as have many predisposing risk factors including race, family history, and previous trauma. Glaucoma has been monitored clinically in the past by careful examination of the optic disc appearance and by visual field testing. Recent advances may allow for earlier diagnosis or earlier detection. Traditional visual field testing has used white on white perimetry; in other words, a white target on a white background using all of the colors of the spectrum to stimulate all three cone types (red, green, and blue). Recent data have suggested that one cone type may be affected earlier or at a more rapid rate in the glaucomatous disease process. This idea led to the development of short wavelength automated perimetry (SWAP), visual field testing that uses blue targets on a yellow background.27,28 Nerve fiber layer analysis is now available using scanning laser technology to detect early subclinical loss of retinal ganglion cells, allowing earlier intervention.29 Traditional treatment approaches have centered on lowering intraocular pressure. Medications have accomplished this by decreasing production of aqueous humour or increasing its outflow from the eye. Surgical approaches have also been designed to shunt fluid from the inside to the outside of the eye and have often led to
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the devastating effects of hypotony and endophthalmitis. Lasers have been used to attempt to open the outflow pathways and avoid these complications with limited success. Trabeculectomy has been the primary surgical procedure, creating a full-thickness opening into the anterior chamber underneath a partial-thickness scleral flap and then suturing the flap closed. Fluid flow is adjusted postoperatively by cutting sutures and slowing the healing responses with topical steroids. More recently 5-FU and mitomycin have been used with success both intraoperatively and postoperatively to delay or halt the healing process.30 Variants of the trabeculectomy technique have also been developed to obtain a more stable pressure lowering effect and lower the risk of infection. Viscocanalostomy is a recently popular technique that involves opening the natural drainage pathways for intraocular fluid using external partial-thickness techniques.31 Secondary surgical procedures have been reserved for failures of traditional medical and surgical treatment. Tube shunts, valved or valveless, connected to reservoirs are inserted and explanted on the eye.32,33 The technical difficulty associated with insertion and the myriad potential postoperative complications have limited their use to recalcitrant glaucoma. Hope has recently emerged for treating glaucoma and limiting its consequences. Neuroprotective agents such as nitric oxide synthetase inhibitors are being investigated.34 If these agents prove to be effective, their use may broaden to treat other forms of optic neuropathy including ischemic and traumatic. In conclusion, ophthalmology is a rapidly evolving surgical and medical field. New advances are being made in all of the subspecialty disciplines that will have lasting social and economic impacts and improve human quality of life. Some of these advances may have potential uses in other medical and surgical specialties.
6. 7. 8. 9.
10. 11. 12. 13. 14. 15. 16. 17.
18. 19. 20. 21. 22.
23. REFERENCES 1. Goldberg RA. Lower blepharoplasty is not about removing skin and fat. Arch Facial Plast Surg 2000;2:22. 2. Edelstein C, Balch K, Shorr N, Goldberg RA. The transeyelid subperiosteal midface-lift in the unhappy postblepharoplasty patient. Semin Ophthalmol 1998;13:107–114. 3. Lucarelli MJ, Khwarg SI, Lemke BN, et al. The anatomy of midfacial ptosis. Ophthal Plast Reconstr Surg 2000;16:7–22. 4. Shorr N, Hoenig JA, Goldberg RA, et al. Fat preservation to rejuvenate the lower eyelid. Arch Facial Plast Surg 1999;1:38–39. 5. Goldberg RA. Transconjunctival orbital fat repositioning: trans-
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position of orbital fat pedicles into a subperiosteal pocket. Plast Reconstr Surg 2000;105:743–748; discussion 749–751. Putterman AM. Intraoperatively controlled small-incision forehead and brow lift. Plast Reconstr Surg 1997;100:262–266. Goldberg RA. Oculoplastic surgeons think mechanically. Arch Ophthalmol 2001;119:756–757. Sires BS, Holds JB, Kincaid MC, Reddi AH. Osteogeninenhanced bone-specific differentiation in hydroxyapatite orbital implants. Ophthal Plast Reconstr Surg 1997;13:244–251. Camara JG, Bengzon AU, Henson RD. The safety and efficacy of mitomycin C in endonasal endoscopic laser-assisted dacryocystorhinostomy. Ophthal Plast Reconstr Surg 2000;16:114– 118. Kao SC, Liao CL, Tseng JH, et al. Dacryocystorhinostomy with intraoperative mitomycin C. Ophthalmology 1997;104:86–91. Kenyon KR, Tseng SCG. Limbal autograft transplantation for ocular surface disorders. Ophthalmology 1989;96:709–722. Tsai RJ, Tseng SC. Human allograft limbal transplantation for corneal surface reconstruction. Cornea 1994;13:389–400. Tan D, Ficker L, Buckley R. Limbal transplantation. Ophthalmology 1996;103:29–36. Helena MC, Meisler D, Wilson SE. Epithelial growth within the lamellar interface after laser in situ keratomileusis (LASIK). Cornea 1997;16:300–305. Salah T, Waring GO, El Maghraby A, et al. Excimer laser in situ keratomileusis under a corneal flap for myopia of 2 to 20 diopters. Am J Ophthalmol 1996;121:143–155. Perez-Santonja JJ, Bellot J, Claramonte P, et al. Laser in situ keratomileusis to correct high myopia. J Cataract Refract Surg 1997;23:372–385. McDonald MB, Carr JD, Frantz JM, et al. Laser in situ keratomileusis for myopia up to ⫺11 diopters with up to ⫺5 diopters of astigmatism with the summit autonomous LADARVision excimer laser system. Ophthalmology 2001;108:309–316. Schanzlin DJ, Asbell PA, Burris TE, Durrie DS. The intrastromal corneal ring segments. Phase II results for the correction of myopia. Ophthalmology 1997;104:1067–1078. Batra VN, McLeod SD. Phakic intraocular lenses. Ophthalmol Clin North Am. 2001;14:335–338. Nanevicz TM, Prince MR, Gawande AA, Puliafito CA. Excimer laser ablation of the lens. Arch Ophthalmol 1986;104:1825– 1829. Duffey RJ, Zabel RW, Lindstrom RL. Multifocal intraocular lenses. J Cataract Refract Surg 1990;16:423–429. Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 1994 9;272:1413–1420. American Academy of Ophthalmology. Photodynamic therapy with verteporfin for age-related macular degeneration. Ophthalmology 2000;107:2314–2317. Machemer R, Steinhorst U. Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration? Graefes Arch Clin Exp Ophthalmol 1993; 231:635–641. Thomas M, Dickinson J, Melberg N, et al. Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophthalmology 1994;101:1384–1396. Algvere P, Berglin L, Gouras P, et al. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol 1994;232:707–716.
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27. Johnson CA, Adams AJ, Casson EJ, Brandt JD. Blue on yellow perimetry can predict the development of glaucomatous visual field loss. Arch Ophthalmol 1993;111:645–650. 28. Stewart WC, Chauhan BC. Newer visual function tests in the evaluation of glaucoma. Surv Ophthalmol 1995;40:119–135. 29. Dreher AW, Reiter K. Retinal laser ellipsometry: A new method for measuring the retinal nerve fiber layer thickness distribution? Clin Vision Sci 1992;7:481. 30. Dreyer EB, Chaturvedi N, Zurakowski D. Effect of MMC and 5-FU supplemented trabeculectomies on the anterior segment. Arch Ophthalmol 1995;113:578–580.
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31. Johnson DH, Johnson M. How does nonpenetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery. J Glaucoma 2001;10:55–67. 32. Krupin T, Podos SM, Becker B, et al. Valve implants in filtering surgery. Am J Ophthalmol 1976;81:232–235. 33. Smith MF, Doyle JW, Sherwood MB. Comparison of the Baerveldt glaucoma implant with the double-plate Molteno. Arch Ophthalmol 1995;113:444–447. 34. Neufeld AH, Hernandez MR, Gonzalez M. Nitric oxide synthase in the human glaucomatous optic nerve head. Arch Ophthalmol 1997;115:497–503.
“What’s New in Surgery” evolves from the contributions of leaders in each of the fields of surgery. In every instance the author has been designated by the appropriate Council from the American College of Surgeons’ Advisory Councils for the Surgical Specialties. This feature is now presented in issues of the Journal throughout the year.
Ophthalmology as a field is characterized by subspecialization. Comprehensive ophthalmologists (“generalists” who do not focus their practice in an ophthalmic subspecialty) continue to represent the majority of practicing ophthalmologists, and their practice typically includes cataract, external ocular disease, including infections and inflammations, glaucoma, and refractive disorders. Advanced medical and surgical problems are typically referred to ophthalmic subspecialists. Nationally, one-fourth of graduating ophthalmology residents go on to fellowship training, and at academic programs, it is not unusual for the majority of the graduating class to pursue subspecialty fellowship training. Especially in urban areas, ophthalmic subspecialists often limit their practice to their subspecialty and do not take care of general problems such as cataract. Currently, organized ophthalmic fellowship training is available in orbitofacial and ophthalmic plastic surgery, retina, cornea and refractive surgery, glaucoma, neurophthalmology, ophthalmic pathology, and pediatric and adult strabismus. Even within the ophthalmic subspecialties, there is a tendency for further specialization. For example, some cornea fellowships, and cornea specialists, focus exclusively on refractive surgery. Orbitofacial and ophthalmic plastic surgery is a broad discipline and there has been a tendency toward additional specialization in aesthetic surgery, lacrimal surgery, and orbital surgery. This update will follow the pattern of subspecialization and focus on developments in the various subspecialties that have most significantly affected patient care, or that have
the greatest potential to affect the care of patients in the future. The political arena: Optometrists seek medical and surgical privileges
One area that has significantly affected ophthalmology in recent years has been ongoing discussion in the political arena regarding the appropriate role of our professional colleagues in optometry. Optometrists are nonphysicians who train in a 3-year program after college. Traditionally, optometrists focused their practice on nonmedical eye screening and refraction (glasses and contact lenses). Some ophthalmologists employ optometrists in their practice to help with patient screening and refraction. As a profession, optometrists seek increasing privileges in patient care, and through well-orchestrated political activities, they have achieved by legislation the ability in most states to independently prescribe oral and topical medications including steroids, antibiotics, antivirals, and narcotics. The training requirements, for example, 6-week pharmacology courses, and oversight for quality of prescribing and practice, are overseen by a board of optometry, independent from the medical board. Optometrists do not complete medical school, medical or surgical internship, or residency training, and at the current time they do not have privileges to perform operations, although there is movement in that direction; for example, in some states optometrists have lobbied for privileges to perform laser surgery. Ophthalmology organizations have taken the position that it requires medical training to best diagnose ophthalmic disease (which is inseparable from systemic disease), to most safely and effectively prescribe medications and perform operations, and to anticipate and recognize potential side effects and complications. The focus of political lobbying has been to emphasize that there is, in
Received July 24, 2001; accepted July 24, 2001. From the Jules Stein Eye Institute, Department of Ophthalmology, UCLA Medical Center, Los Angeles, CA. Correspondence address: Norman Shorr, MD, FACS, 435 N Roxbury Dr, Suite 104, Beverly Hills, CA 90210.
© 2001 by the American College of Surgeons Published by Elsevier Science Inc.
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fact, enormous value in the intense didactic, practical, and ethical training that is encompassed by medical school, internship, and residency training, and that the issue at hand is not primarily professional economic rivalry, but protection of the public. Orbitofacial and ophthalmic plastic surgery: Enlarging in a time of contraction
Oculoplastic surgery is a relatively young subspecialty. In the 1960s, some ophthalmologists sat around a restaurant table discussing the value of forming an organized subspecialty group of ophthalmologists who were interested in plastic surgery around the eye. Early on, the field of oculoplastics was small both in terms of numbers (there were just a handful of fellowships) and scope. Fellowships were 6 months. It was rare to find oculoplastic surgeons who limited their practice to oculoplastics. For the most part, oculoplastic surgeons focused on a limited number of surgical procedures and problems, and there was not much interest in extending outside the orbit complex. The field has exploded since that time and is evolving into a broader discipline that, echoing the discipline of maxillofacial surgery, might best be called orbitofacial surgery. There are now more than 400 members of ASOPRS (the American Society of Ophthalmic Plastic and Reconstructive Surgery) and fellowships are 2 years long, with many fellows taking additional subsubspecialty training after 2 years of fellowship. The result of this massive influx of intellectual talent has been a blossoming of research and education that has enormously expanded our knowledge of anatomy and function of the orbit, eyelid, and face. Starting from the nucleus of the eye, arguably the most important functional and esthetic structure of the face, orbitofacial fellowship programs now take advantage of increased time and increased knowledge to train fellows in a wide range of anatomic and surgical principles involving the extended orbital bony complex and the extended eyelid complex, including the eyebrow and midface. A small group of oculoplastic surgeons have been doing facelifts for many years (for example, in the 1997 Wendell Hughes lecture at the American Academy of Ophthalmology, Henry Baylis summarized a 15-year experience) and increasing numbers of ASOPRS-approved fellowships are offering or plan to offer facelift training as part of the fellowship curriculum. Ophthalmology-trained orbitofacial surgeons have a
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great deal to contribute to the field of esthetic and reconstructive facial surgery. The extended eyelid complex, including the eyebrow and forehead superiorly and midface inferiorly, is the focal point of the entire face, both functionally and esthetically. Attention to and correction of the midface and lower eyelid contour has replaced the now outdated ideas of blepharoplasty to remove excess skin, muscle, and fat.1 Rather than tightening laterally through a preauricular incision, the midface, which descends inferiorly, is more appropriately elevated superiorly. It is best addressed in conjunction with, and typically through, the same incision as the lower eyelid rejuvenation. So midface lifting, which is the single most important aspect of midface and facelift contouring, falls directly into the responsibility of the eyelid surgeon.2 Excellent thinkers from many disciplines have helped define the anatomy and function of these anatomic structures, but certainly some of the pivotal and innovative contributions have come from ophthalmology. An example of the unique anatomic and philosophic perspective that ophthalmic-trained orbitofacial surgeons bring to facial surgery is the anatomic description of the midfacial orbital ligaments and depressor supracilli muscle by Lucarelli and colleagues.3 Orbital facial esthetic surgery focuses increasingly on small incision and nonincisional techniques. No group is more conservative or reverent to eyelid function than ophthalmologists, who for years have had to manage some of the worst complications of traditional blepharoplasty techniques. Older techniques of blepharoplasty that focused on excision of skin, muscle, and fat were destructive not only to eyelid function, sometimes with disastrous results, but also to the esthetic beauty of the eyelid complex. Look in any celebrity magazine for examples of surgical-appearing eyelids, with hollowappearing orbit and change in shape of the eyelid aperture. Newer concepts of fat preservation,4 fat repositioning,5 conservative sculpture, minimal skin and muscle removal,1 and small-incision surgery for the forehead6 and midface have contributed to the field of esthetic facial surgery not only in reduced functional complications, but also in improved, more natural esthetic results. Ophthalmologists introduced botulinum toxin to the medical community in the 1980s as a treatment for strabismus and blepharospasm. Oculoplastic surgeons began using botulinum toxin for esthetic purposes in the early 1990s. Botulinum toxin treatment for wrinkles,
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facial asymmetry, frown lines, and undesired dynamic irregularities is now extremely popular, and practiced by physicians from a number of disciplines including plastic surgery, facial plastic surgery, and dermatology. It is probably the single most important advance in esthetic facial surgery of the last decade because it offers a noninvasive technique to address concerns that previously would have been treated surgically, often with less predictable and certainly less reversible results. Facial anatomy and surgical techniques are covered in the ophthalmology residency, and increasing numbers of programs offer significant exposure to esthetic surgery during the residency, but in reality most ophthalmology residents, just like residents coming from other specialties, will want to take additional training in esthetic surgery to feel confident in this rapidly expanding discipline. This training will typically involve 2 years of oculoplastic fellowship and then often additional training in esthetic reconstructive orbitofacial surgery. Ophthalmic-trained orbitofacial surgeons are not the only subspecialists with expertise in esthetic and reconstructive surgery of the face. As physicians from many training backgrounds enter the field of esthetic surgery, the public is best protected by establishing crossdisciplinary standards for board certification and board equivalency. Currently the issue of credentialing for esthetic facial surgery is in evolution. A physician and surgeon’s license entitles one to operate on the face from a legal standpoint. Hospital staffs control what is done by various specialties in the hospital operating rooms, but there is currently little state and no federal regulation of procedures done in an office setting. Although the American Society of Ophthalmic Plastic and Reconstructive Surgery requires for Fellowship a written and oral examination and completion of an approved postresidency training program, ophthalmic plastic surgery is not recognized as a specialty by the American Board of Medical Specialties. A number of ophthalmology-trained orbitofacial surgeons have now successfully sat for the American Board of Cosmetic Surgery, a crossdisciplinary credentialing organization. Like all disciplines that incorporate plastic and reconstructive surgery, ophthalmic plastic surgery meetings and journals are characterized by a preponderance of mechanical papers that discuss iterative adjustments to previous anatomic or surgical ideas; not infrequently, a careful review of the ancient medical literature (before
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1966, we mean) reveals that the idea was already thought of and forgotten. This is not to belittle those innovative surgeons who continue to try to refine our current anatomic and mechanical concepts. Rather, it reflects the fact that reconstructive surgery is straining at the bounds of its ability to get much better based on current technology. The great breakthroughs of the future will not be mechanical, but rather biological. It is our inability to control wound healing that most severely limits our results.7 New work in growth factors to increase the revascularization of orbital implants8 is an excellent example of the ability of this nascent technology to improve our ability to help patients with surgery. Often, the ability not to encourage but rather to discourage the body’s natural healing response is critical to successful surgical outcomes. One of the best examples of the successful application of biologic agents to attenuate unwanted wound healing response is the use of mitomycin-C. Mitomycin-C has been used by ophthalmologists to prevent closure of the fistula created on the eyeball to lower the pressure in glaucoma surgery. More recently, in the discipline of lacrimal surgery, mitomycin-C has been used to prevent closure of the newly created ostium in dacryocystorhinostomy. An increasing body of experimental and clinical data9,10 suggests that application of mitomycin-C solution, 0.4 mg per mL, to the newly created surgical opening successfully tipped the balance of biologic forces toward maintaining, rather than closing, the ostium. The surgical principle embodied by this work should be applicable to a number of surgical disciplines. Cornea and refractive surgery
The cornea is the body’s clear window to the world and is made up of many layers, each with different functions. Severe corneal epithelial disease results in blurred vision because of a loss of clear refracting media. Corneal epithelial cells are produced from stem cells that are located at the limbus (the junction of the white and clear areas of the eye). Once stem cells are lost the corneal epithelial cells are replaced by conjunctival epithelial cells, which do not provide clear refractive media. Limbal stem cell transplantation is a new technique offering hope of visual recovery to patients with severe corneal epithelial surface disease.11 Autografts are used in cases of severe unilateral disease or bilateral cases with relative sparing of one eye and have the advantage of not requiring immunosuppression. Allografts from living related do-
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nors12 or cadavers13 have also been used with limited success with immunosuppression. Refractive surgery involves manipulating the eye to overcome its inherent inability to focus light on the retina, ie, nearsightedness, farsightedness, and astigmatism. Keratorefractive surgery involves changing the shape of the cornea to overcome inherent refractive errors. Older techniques (RK, radial keratotomy) accomplished this by making incisions in the cornea to flatten or steepen it to achieve clear vision without the need for corrective lenses. More recently lasers have been used to ablate the cornea in predetermined areas to achieve the same effect. PRK (photorefractive keratotomy) accomplishes this by first scraping off the corneal epithelium and then applying laser ablation to the corneal stroma. Visual recovery takes days to weeks as the corneal epithelium heals over the ablated corneal stromal bed. LASIK (laser-assisted in situ keratomileusis) is like PRK in that a laser is used to ablate the corneal stroma, but instead of scraping off the corneal epithelium, a hinged flap of cornea is created with a keratome. Keratomes differ in design; some are manual and some are automatic. Some cut in a straight line and others cut while rotating on an axis. All share common features including a suction system that couples the eye to the keratome. Corneal flap creation is not without problems. Commonly reported complications include free flaps (caps), incomplete flaps, flap striae, ablation of flap hinges, epithelialization under flaps, microbial keratitis, and dry eyes.14-16 Once the flap is created it is displaced out of the laser field during the ablation and then replaced to its original position. Remarkably, after careful replacement and adequate drying (minutes) the corneal flap is stable and visual recovery is, in most cases, nearly instantaneous. Historically, accurate laser ablation of the corneal stroma required careful, steady patient ocular fixation in order to achieve predictable ablation. Poor postoperative results have been attributed to loss of or poor intraoperative visual fixation. Laser design and failure to calibrate the laser to compensate for temperature and humidity have also led to poor postoperative results. New technology attempts to overcome these problems. Gaze tracking systems now allow the laser to ablate cornea only when the patient is optimally fixated and even allow patients with nystagmus to undergo refractive surgery.17 Protocols now require more than daily calibration. Wave front technology may allow for custom corneal ablation in-
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stead of the current one size fits all approach, which may improve results to better than 20/20. Other techniques are also being used to overcome the inherent refractive error of the eye. Corneal stromal rings (Intacs) are another keratorefractive technique for changing the shape of the cornea.18 Thought to be reversible, this technique involves making a vertical, partial thickness incision into the cornea. A special keratome is used to create arcuate intrastromal tunnels into which clear polymethyl methacrylate, half ring-shaped implants are introduced. This technique is also fraught with potential complications including microbial keratitis and under- or overcorrections. Phakic intraocular lens implantation capitalizes on familiar techniques used in cataract surgery to introduce an artificial lens inside the phakic eye.19 Ironically, a cataract can result, requiring further surgical correction. Other potential devastating complications include endophthalmitis and glaucoma. Although most patients are able to improve their ability to read the eye chart after refractive surgery, many successfully treated patients suffer from other effects of the procedure that can be debilitating and irreversible, including loss of contrast sensitivity and nyctalopia. Careful preoperative evaluation of patients can avoid many potential surgical complications and identify those predisposed to difficulty with the effects of surgery. Cataract surgery
Successful cataract surgery involves removal of a cloudy lens and replacement with an artificial lens. Most procedures are done on an outpatient basis under local or topical anesthesia. Removal of the lens nucleus and cortex from within the lens capsule is accomplished with ultrasonic emulsification (phacoemulsification) and suction. Alternatives to ultrasonic emulsification are being developed, including laser ablation of the lens,20 but are currently not used in clinical practice in the United States. Intraocular lenses are positioned in the remaining capsular bag; there they remain static, uncoupled to the intrinsic focusing mechanism of the eye. Consequently, the eye focuses at one distance, predictable by careful preoperative measurements, and the patient is left wearing corrective lenses to see clearly at other distances. Another strategy for overcoming this is “monovision correction,” which involves correcting one eye for distance and one eye for near. This has been accepted with varying results. Recently, multifocal intraocular lenses
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have been developed and implanted, overcoming the near-distance discrepancy by having zones of differing focusing power in the lens. So a patient is able to see clearly at all distances without requiring additional lenses under most viewing conditions. The multifocal design is responsible for much of the disfavor with this form of correction. Lens-edge effect as well as zone-edge effect have led to difficulty with glare and contrast sensitivity in some patients.21 Other techniques for coupling an intraocular lens to the inherent focusing mechanism of the eye are currently being investigated but are not used in clinical practice. Retinal disease and surgery
Age-related macular degeneration (AMD) distorts and sometimes robs elderly patients of their central vision. This feared disease has until recently been a visual death sentence with permanent social and economic sequelae. AMD comes in two forms, both only affecting the anatomic spot responsible for central vision called the macula. The dry form, which is the most common, usually leads to slow distortion of central vision. Clinically it is identified by deposition of waste products in the layers underneath the retina called the retinal pigment epithelium and Bruch’s membrane. These two layers are to the eye what the liver is to the body. The wet form of AMD involves a break in the retinal pigment epithelium and Bruch’s membrane, allowing neovascular membranes to invade and distort the retina. The consequence of these membranes is central blindness. Unfortunately, laser coagulation of these membranes has been hampered by collateral damage (a permanent blind spot in the treatment area) and recurrence, usually in a worse anatomic position. Past enthusiasm has centered on antioxidant supplementation as an attempt to halt or slow the degeneration,22,23 potentially preventing the normal to dry to wet progression. Recently a new therapy combining laser technology with photosensitizing drugs has shown some benefit in treating wet AMD.23 Photodynamic therapy involves giving patients an intravenous photosensitizing drug (verteporfin) and then treating the eye with lowpowered laser over a long duration. This technique has been shown to selectively coagulate certain types of neovascular membranes with minimal collateral damage. The downside of this therapy has been modest visual improvement at best, and the need for multiple retreatments as often as every 3 months. The cost for each
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treatment is currently more than $1,000 just for the drug, and this will certainly become a larger issue in the years to come. Other new alternatives for patients who have already lost central vision from AMD are to physically move the retina to an overlying area of normal retinal pigment epithelium and Bruch’s membrane24 or to surgically remove the neovascular membrane.25 Macular translocation surgery accomplishes this by first cutting the retina, detaching it, and reattaching it to an area with healthy underlying tissue. Submacular surgery involves retinotomy, detachment of the retina, removal of the membrane, and reattachment of the retina. Visual results have varied and complications have been reported. A technique that may prove beneficial in the future is retinal pigment epithelial transplantation.26 Glaucoma
Glaucoma is a neuropathy of the optic nerve leading to loss of peripheral and later central vision with characteristic clinical changes in the optic nerve head. High intraocular pressure has historically been synonymous with glaucoma. But other forms of glaucoma not associated with high intraocular pressure have been identified, as have many predisposing risk factors including race, family history, and previous trauma. Glaucoma has been monitored clinically in the past by careful examination of the optic disc appearance and by visual field testing. Recent advances may allow for earlier diagnosis or earlier detection. Traditional visual field testing has used white on white perimetry; in other words, a white target on a white background using all of the colors of the spectrum to stimulate all three cone types (red, green, and blue). Recent data have suggested that one cone type may be affected earlier or at a more rapid rate in the glaucomatous disease process. This idea led to the development of short wavelength automated perimetry (SWAP), visual field testing that uses blue targets on a yellow background.27,28 Nerve fiber layer analysis is now available using scanning laser technology to detect early subclinical loss of retinal ganglion cells, allowing earlier intervention.29 Traditional treatment approaches have centered on lowering intraocular pressure. Medications have accomplished this by decreasing production of aqueous humour or increasing its outflow from the eye. Surgical approaches have also been designed to shunt fluid from the inside to the outside of the eye and have often led to
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the devastating effects of hypotony and endophthalmitis. Lasers have been used to attempt to open the outflow pathways and avoid these complications with limited success. Trabeculectomy has been the primary surgical procedure, creating a full-thickness opening into the anterior chamber underneath a partial-thickness scleral flap and then suturing the flap closed. Fluid flow is adjusted postoperatively by cutting sutures and slowing the healing responses with topical steroids. More recently 5-FU and mitomycin have been used with success both intraoperatively and postoperatively to delay or halt the healing process.30 Variants of the trabeculectomy technique have also been developed to obtain a more stable pressure lowering effect and lower the risk of infection. Viscocanalostomy is a recently popular technique that involves opening the natural drainage pathways for intraocular fluid using external partial-thickness techniques.31 Secondary surgical procedures have been reserved for failures of traditional medical and surgical treatment. Tube shunts, valved or valveless, connected to reservoirs are inserted and explanted on the eye.32,33 The technical difficulty associated with insertion and the myriad potential postoperative complications have limited their use to recalcitrant glaucoma. Hope has recently emerged for treating glaucoma and limiting its consequences. Neuroprotective agents such as nitric oxide synthetase inhibitors are being investigated.34 If these agents prove to be effective, their use may broaden to treat other forms of optic neuropathy including ischemic and traumatic. In conclusion, ophthalmology is a rapidly evolving surgical and medical field. New advances are being made in all of the subspecialty disciplines that will have lasting social and economic impacts and improve human quality of life. Some of these advances may have potential uses in other medical and surgical specialties.
6. 7. 8. 9.
10. 11. 12. 13. 14. 15. 16. 17.
18. 19. 20. 21. 22.
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position of orbital fat pedicles into a subperiosteal pocket. Plast Reconstr Surg 2000;105:743–748; discussion 749–751. Putterman AM. Intraoperatively controlled small-incision forehead and brow lift. Plast Reconstr Surg 1997;100:262–266. Goldberg RA. Oculoplastic surgeons think mechanically. Arch Ophthalmol 2001;119:756–757. Sires BS, Holds JB, Kincaid MC, Reddi AH. Osteogeninenhanced bone-specific differentiation in hydroxyapatite orbital implants. Ophthal Plast Reconstr Surg 1997;13:244–251. Camara JG, Bengzon AU, Henson RD. The safety and efficacy of mitomycin C in endonasal endoscopic laser-assisted dacryocystorhinostomy. Ophthal Plast Reconstr Surg 2000;16:114– 118. Kao SC, Liao CL, Tseng JH, et al. Dacryocystorhinostomy with intraoperative mitomycin C. Ophthalmology 1997;104:86–91. Kenyon KR, Tseng SCG. Limbal autograft transplantation for ocular surface disorders. Ophthalmology 1989;96:709–722. Tsai RJ, Tseng SC. Human allograft limbal transplantation for corneal surface reconstruction. Cornea 1994;13:389–400. Tan D, Ficker L, Buckley R. Limbal transplantation. Ophthalmology 1996;103:29–36. Helena MC, Meisler D, Wilson SE. Epithelial growth within the lamellar interface after laser in situ keratomileusis (LASIK). Cornea 1997;16:300–305. Salah T, Waring GO, El Maghraby A, et al. Excimer laser in situ keratomileusis under a corneal flap for myopia of 2 to 20 diopters. Am J Ophthalmol 1996;121:143–155. Perez-Santonja JJ, Bellot J, Claramonte P, et al. Laser in situ keratomileusis to correct high myopia. J Cataract Refract Surg 1997;23:372–385. McDonald MB, Carr JD, Frantz JM, et al. Laser in situ keratomileusis for myopia up to ⫺11 diopters with up to ⫺5 diopters of astigmatism with the summit autonomous LADARVision excimer laser system. Ophthalmology 2001;108:309–316. Schanzlin DJ, Asbell PA, Burris TE, Durrie DS. The intrastromal corneal ring segments. Phase II results for the correction of myopia. Ophthalmology 1997;104:1067–1078. Batra VN, McLeod SD. Phakic intraocular lenses. Ophthalmol Clin North Am. 2001;14:335–338. Nanevicz TM, Prince MR, Gawande AA, Puliafito CA. Excimer laser ablation of the lens. Arch Ophthalmol 1986;104:1825– 1829. Duffey RJ, Zabel RW, Lindstrom RL. Multifocal intraocular lenses. J Cataract Refract Surg 1990;16:423–429. Seddon JM, Ajani UA, Sperduto RD, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 1994 9;272:1413–1420. American Academy of Ophthalmology. Photodynamic therapy with verteporfin for age-related macular degeneration. Ophthalmology 2000;107:2314–2317. Machemer R, Steinhorst U. Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration? Graefes Arch Clin Exp Ophthalmol 1993; 231:635–641. Thomas M, Dickinson J, Melberg N, et al. Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophthalmology 1994;101:1384–1396. Algvere P, Berglin L, Gouras P, et al. Transplantation of fetal retinal pigment epithelium in age-related macular degeneration with subfoveal neovascularization. Graefes Arch Clin Exp Ophthalmol 1994;232:707–716.
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27. Johnson CA, Adams AJ, Casson EJ, Brandt JD. Blue on yellow perimetry can predict the development of glaucomatous visual field loss. Arch Ophthalmol 1993;111:645–650. 28. Stewart WC, Chauhan BC. Newer visual function tests in the evaluation of glaucoma. Surv Ophthalmol 1995;40:119–135. 29. Dreher AW, Reiter K. Retinal laser ellipsometry: A new method for measuring the retinal nerve fiber layer thickness distribution? Clin Vision Sci 1992;7:481. 30. Dreyer EB, Chaturvedi N, Zurakowski D. Effect of MMC and 5-FU supplemented trabeculectomies on the anterior segment. Arch Ophthalmol 1995;113:578–580.
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31. Johnson DH, Johnson M. How does nonpenetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery. J Glaucoma 2001;10:55–67. 32. Krupin T, Podos SM, Becker B, et al. Valve implants in filtering surgery. Am J Ophthalmol 1976;81:232–235. 33. Smith MF, Doyle JW, Sherwood MB. Comparison of the Baerveldt glaucoma implant with the double-plate Molteno. Arch Ophthalmol 1995;113:444–447. 34. Neufeld AH, Hernandez MR, Gonzalez M. Nitric oxide synthase in the human glaucomatous optic nerve head. Arch Ophthalmol 1997;115:497–503.