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Title The interplay of genetics and surgery in ophthalmic care.

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Journal Seminars in , 10(4)

ISSN 0882-0538

Author Gorin, MB

Publication Date 1995-12-01

DOI 10.3109/08820539509063801

Peer reviewed

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The Interplay of Genetics and Surgery in Ophthalmic Care

Michael B. Gorin

To cite this article: Michael B. Gorin (1995) The Interplay of Genetics and Surgery in Ophthalmic Care, Seminars in Ophthalmology, 10:4, 303-317, DOI: 10.3109/08820539509063801 To link to this article: http://dx.doi.org/10.3109/08820539509063801

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Download by: [UCLA Library] Date: 02 May 2017, At: 14:05 The Interplay of Genetics and Surgery in Ophthalmic Care

Michael 6. Gorin

LTHOUGH ONLY a minor component of dures. Genetic conditions that affect the eye A the surgical volume of ophthalmic care, directly may also affect the surgicaI outcomes of genetic disorders are among the most challeng- routine procedures. The coexistence of Fuch’s ing cases for the ophthalmic surgeon. Ophthal- endothelial dystrophy in patients undergoing mic surgery may be indicated to address specific routine extraction can contribute to aspects of heritable disorders that involve the postoperative corneal edema. Refractive sur- failure of proper development and function of gery in individuals with unsuspected keratoco- ocular structures or the disruption of normal nus has resulted in unsatisfactory results and tissues by genetically determined abnormalities, progressive and .’ Sickle cell such as tumors or degenerative conditions. Cra- disease and trait are risk factors for anterior niosynostoses, hereditary , congenital stra- segment ischemia in scleral buckling surgery bismus, corneal dystrophies, juvenile , and extraocular muscle surgery.* Although each congenital , dislocated lenses, retinal of these genetic conditions is uncommon or tumors (retinoblastomas and hemangiomas), rare, the widespread prevalence of , and sickle cell are examples of cataract, retinal, and refractive surgery make it ophthalmic genetic conditions that frequently highly likely that these patients will be encoun- require surgical management. The ophthalmolo- tered. In addition, as we come to recognize that gist may be called on to manage the secondary genetics can play more subtle roles in physiologi- complications of genetic disorders such as expo- cal responses, there is the potential for anticipat- sure problems related to facial paralysis after ing those patients who will be at an increased removal of acoustic neuromas, ocular exposure risk of experiencing adverse responses to oph- from dysautonomias, or strabismus from the thalmic surgery. We will review this aspect of ocular fibrosis syndromes. In this overview of genetics to provide the clinician with guidelines ophthalmic surgery and genetics we will con- toward avoiding surgical complications from sider the surgical management of ophthalmic familial disorders. genetic disorders, the potential impact of genet- SURGICAL MANAGEMENT OF OCULAR ics on ophthalmic surgery, and those conditions GENETIC DISORDERS that require special attention by the surgeon. In most instances, articles regarding the surgical For a number of genetic disorders, ocular management of genetic disorders are limited to surgery is well established and the treatment of case reports and small surgical series. The rarity choice. There is a considerable amount of of most conditions precludes controlled clinical literature addressing surgical methods for rou- studies. I have included extensive references tine strabismus and for more difficult eye align- that address surgical issues so that the reader ment problems such as Duane’s syndrome. Simi- can further explore specific disorders that are larly, the treatment of ^,^-^ only briefly mentioned in this overview. congenital pt~sis,’,~ reconstruction,”Il and Limited attention has been directed to the congenital or juvenile glaucoma’*-’*has been impact of genetic conditions on routine ophthal- described extensively. There are a number of mic surgery. Surgeons, patients, and health care rarer genetic disorders that pose additional payors continue to have increasing expectations potential challenges for the surgeon and pa- for uncomplicated and successful ophthalmic procedures. It is increasingly important to iden- From the Departments of Ophthalmology and Human tify underlying issues that may affect intraopera- Genetics, University of Pittsburgh School of Medicine and tive safety and surgical outcomes. There are Graduate School of Public Health, Pittsburgh, PA. genetic factors and conditions that affect an Address reprint requests to Michael B. Gorin, MD, Depart- ment of Ophthalmology, The Eye & Ear Institute Building, 203 individual’s response to medications, anesthe- Lorhrop St, Pittsburgh, PA 15213. sia, pain, and wound healing that can greatly Copyright 0 1995 by W.B. Saunders Company alter the outcomes of routine ophthalmic proce- 088282-053819511004-0005$5.00lO

Seminars in Ophthalmology, Vol 10, No 4 (December), 1995: pp 303-317 303 304 MICHAEL 8. GORlN

tient. These disorders serve as examples of why giomas, treatment is indicated when visual devel- the ophthalmologist must consider the unique opment and function are threatened. The impact of each genetic condition on ocular and natural history of these lesions frequently in- systemic anatomy and physiology. cludes spontaneous involution, although a num- ber of interventions including corticosteroid Orbital Surgery for Craniodysostosis and interferon injections have been ~sed.~')-~' Recently found to be caused by mutations in The majority of hemangiomas are sporadic, the FGFR2 and FGFRl genes, Crouzon's syn- although familial forms have been reported. drome and Pfeiffer Syndrome are part of a The ophthalmic surgeon, in addition to establish- group of autosomal dominant disorders collec- ing the anatomic extent of the lesion or lesions tively known as the craniosynostoses. These that affect the lid and , should take the conditions are characterized by the premature appropriate steps to ensure that other systemic fusion of the cranial sutures creating marked and central nervous system (CNS) manifesta- deformities of the head including hypertelorism tions are not overlooked. If an individual is and laterally displaced orbits. Rarely, prema- found to have multiple hemangiomas (orbital, ture fusion of the metopic suture (less than 10% intraocular, visceral, or in the CNS), then other of craniosynostosis cases) results in close-set family members should be contacted and evalu- eyes.1y.20Oculoplastic surgeons, as well as maxil- ated. lofacial, plastic, and neurosurgeons, have suc- In the case of neurofibromas, surgical exci- cessfully tackled the surgical challenges of this sion is difficult because of the plexiform nature genetic condition.21 Three-dimensional com- of the lesion with the potential for damage to puted tomography imaging and multidisci- normal tissues. Lesions often extend beyond the plinary surgical teams have enhanced the surgi- orbit and can encroach on the brain. Intracra- cal o~tcomes.~~-~~ compression from nial approaches may be required and partial bony malformations and from in- resections have had generally disappointing re- creased intracranial pressure have been re- sults because of recurrence and enlargement of ported. Strabismus is not uncommon in these the neurofibr~mas.~~-~~ patients, and extraocular muscle surgery may be A great deal has been written regarding the required. The surgeon may encounter abnormaI repair of congenital ptosis syndr~mes.~JDuke- muscle insertions during traditional recession Elder has cited eight major categories of con- or resection procedures that may alter the genital pto~is,~"seven of which represent famil- surgical response. Neurofibromatosis type I can ial forms. The identification of unilateral or also cause significant orbital deformities with bilateral congenital ptosis in a patient should bony erosion and unilateral proptosis. The sur- prompt an effort to identify other potential gical issues regarding this disorder are ad- family members. The key aspects to surgical dressed in the following section on lid surgery. repair are the residual amount of levator func- tion, the extent to which the eye has a normal Lid Surgery Bell's phenomenon, the progressive or station- The principal goals of lid surgery are to ary nature of the underlying disorder, and the protect the eye, prevent occlusion or induced potential of associated abnormalities that may anisometropic , ensure normal visual compromise the integrity of the eye.7,8-41,42Some function, and re-establish a normal facial appear- ptosis may be protective for eyes that lack an ance. Serious malformations of eyelid develop- adequate Bell's phenomenon. Poor tear produc- ment may be isolated or part of more complex tion (congenital Horners, ectodermal dyspla- genetic syndromes. Repair of these abnormali- sias) or corneal hypesthesia can seriously com- ties is es~ential,"~~-*~-~~but the ophthalmologist promise the outcome of even minor lid must also be aware of other associated abnor- procedure^.^'-^^ This can even be true if the malities for each individual and condition. surgical candidate appears to be minimally af- Among the most common genetic deformities fected by the disorder under normal circum- are hemangiomas of the and neurofibro- stances. A striking example of this situation was mas from neurofibromatosis type I. For heman- a woman whose child had ectodermal dysplasia. THE INTERPLAY OF GENETICS AND SURGERY 305

The mother had been found to be mildly af- comitant squints, with or without the presence fected with the disorder only after her child had of ptosis, to ensure that underlying genetic been diagnosed. Her mild dental anomalies had causes are established. The ophthalmologist been surgically corrected, thus obscuring any should consult with the pediatrician and geneti- obvious manifestations of the disorder, and she cist about hematologic disorders, factors that worked successfully as a professional model. may affect anesthesia or wound healing, and Unfortunately, after undergoing cosmetic other neurological findings that may affect vi- blepharoplasties by a plastic surgeon, she was sual function. plagued by continuous problems of eye pain and Isaacs and Barlow" described a family with exposure difficulties, even though the surgical malignant hyperthermia and dysmorphic fea- correction had been modest and the cosmetic tures that included scoliosis, ptosis, strabismus, result had been a success. dislocation of the shoulders and patellas, pes In some instances, metabolic disturbances cavus, pectus deformity, below average IQ, and associated with some cases of congenital ptosis increased creatine kinase. These features were can substantially increase the risk of undergoing transmitted in an autosomal dominant pattern. general anesthe~ia.~'.~~ Strabismus can be observed in association with several congenital myopathies, and in all cases there is probably an increased risk of malignant Congenital strabismus has long been recog- hyperthermia.sx Given the potentially fatal out- nized to have a significant genetic component.4y comes of anesthesia-induced malignant hyper- Patching for amblyopia and surgical manage- thermia, every effort should be made to recog- ment have remained the mainstay of treatment. nize the patient who is at increased risk before Botulinum toxin has become a more recent administering general anesthesia for strabismus addition to the therapy of extraocular muscle surgery. imbalances. The ocular fibrosis syndrome poses Strabismus is frequently seen in oculocutane- a special challenge to the ~urgeon.~",~~Both the ous albinism. Rare forms of oculocutaneous muscles and extraocular tissues are markedly albinism are associated with bleeding disorders fibrosed and abnormal, the is often (Hermansky-Pudlak syndrome) or immunodefi- friable, and the normal guidelines for recession ciency (Chediak Higashi syndrome). The Her- and resection are often ineffective. In cases of mansky-Pudlak syndrome is particularly com- Mobius syndrome the severe second- mon in the Puerto Rican population. Any ary to cranial IV nerve palsy can greatly limit underlying form of oculocutaneous albinism, the range of aligned visual field.sZ-56Traboulsi even when the hypopigmentation is minimal, and Maumenees5 reported bilateral medial and can have a bearing on the long-term success of lateral recti aplasia in at least one case of binocular alignment caused by the CNS develop- Mobius syndrome. A range in the integrity of mental abnormalities associated with these con- the extraocular musculature occurs in this disor- ditions. der and the ophthalmic surgeon must be pre- pared to adapt the surgical corrections accord- Comeat Surgety ingly. There are many autosomal dominant and Strabismus is a frequent finding in a spectrum recessive dystrophies affecting every layer of the of genetic disorders. Strabismus in the presence . Although some of these conditions are of dysmorphic facial features warrants a genetic relatively benign, others are major causes of diagnosis before surgery. Like congenital ptosis, and ocular discomfort. Cor- strabismus is frequently observed in patients neal clouding can result from systemic disor- with progressive myopathies and ophthalmople- ders, such as the mucopolysaccharidoses, and gias. The progressive nature of these disorders from cornea-specific dystrophies. Corneal dys- clearly affects the benefits of ocular realignment trophies represent an important indication for and may suggest the presence of other underly- penetrating keratoplasties and will comprise an ing metabolic disorders.4HThe clinician must be increasing percentage of cases as the number of especially vigilant in evaluating atraumatic, non- pseudophakic bullous keratopathy cases de- 306 MICHAEL B. GORlN

crease^.^^-^^ Although penetrating keratoplasties IV were initially reported to have some suc- have a high success rate of graft survival, recur- cess122and partial corneal clearing has been rent disease is freq~ent.~”~~Lamellar kerato- reported in response to bone marrow and tissue plasties have been used for several corneal transplants,1”0~-’02~-’”~and there is evidence that dy~trophies,~’-~~and recent work has indicated cysteamine drops are capable of slowing and that excimer laser photokeratectomy may be a potentially reversing the early stages of accumu- viable alternative to penetrating keratoplasty or lation of corneal crystals in nephropathic cysti- superficial keratectomy for some of the superfi- nosis.105-107J11The combination of medications cial corneal dystrophie~.~~-~~Current surgical and/or gene therapy in conjunction with cor- experience is insufficient to determine the rate neal surgery may be invaluable for maintaining and severity of disease recurrence using photo- the long-term clarity of grafts for progressive keratectomy procedures. Table 1 summarizes metabolic and corneal disorders. the reported procedures for the treatment of is a special case of the corneal different corneal dystrophies. dystrophies because its initial manifestations Some of the genetic conditions associated may be subtle with mild to moderate astigma- with corneal opacities that require corneal trans- tism and myopic . Keratoconus plants include sclerocornea,IL2Peter’s anomaly can be transmitted in an autosomal dominant (either genetic or in association with fetal alco- fashion in the absence of other abnormalities, hol syndrome),””-’l9 ,I2O and lysosomal or it can occur sporadically. It may be associated storage disease^.^^^^^^^^'^ The major determinant with other genetic conditions such as Down’s in the success of these grafts is the presence of syndrome, Ehlers-Danlos Syndrome IV, and other ocular abnormalities, most notably glau- Leber’s congenital amaurosis. Keratoconus is coma.121 one of the indications for penetrating kerato- Alternative approaches to the treatment of plasty with the highest graft survival rate.60Jjy,y7 corneal opacities from ongoing metabolic and There have been several case reports in which genetic conditions have been attempted. Con- early keratoconus was overlooked and these junctival grafts to treat mucopolysaccharidosis patients underwent refractive surgical proce-

Table 1. Major Corneal DystrophiesTreated With Surgical Intervention Procedures

1234R Basement membrane dystrophies X X Recurrent erosions were predominant symptoms in younger (unspecified) patients whereas older patients had decreased vision.73.75.83 Reis Bucklers X xx References 65, 77-80, 82,84,85 Meesmann’s X Reference 82 Map-dot-fingerprint X These cases may be genetic or nongenetic causes.82 Granular xxxx The high rate of recurrence has led some to recommend lamellar procedure to avoid multiple full-thickness grafts.60,61.’0.72.86-88 Gelatinous xx Reference 89 Crystalline dystrophy (Schnyder) X Reference 82 Lattice (type I and type 11) xx References 61,63,68,82 Macular xx X References 61, 64,71, 74 Avellino X References 81, 90 Fuchs Endothelial X Subepithelial fibrosis has been treated in at least one case with photokeratectomy.60~61~67~69~y1-y3 Posterior polyrnorphous X X Primary causes of graft failure are glaucoma and retrocorneal membranes. Histological confirmation of recurrence has been reported.59.6634 Corneal edema of Maumenee X Reference 95 Keratoconus X References 60,69,96,97 Lysosomal storage diseases xx Corneal clearing has been reported with some systemic therapies for these disorders.98-104 Cystinosis xx Cysteamine eyedrops work primarily in preventive capacity and longstanding opacities are not eliminated.105-111 Procedures: 1-Superficial excisional keratectomy/basementmembranectomy, 2-Photoablative keratectomy (excimer), 3-Lamel- lar keratoplasty, 3-Lamellar keratoplasty, 4-Penetrating karatoplasty, R-Recurrences reported. THE INTERPLAY OF GENETICS AND SURGERY 307

d~res.~x~~~J~~The complications of refractive cases, particularly patients with aniridia, cor- surgery in these patients included rapid progres- neal problems, such as often sion of corneal astigmatism and acceleration of limit the use of these lenses. For traumatic and corneal decompensation. The poorer prognosis hereditary aniridia there have been efforts to of refractive surgery for keratoconus should use an artificial diaphragm as part of an intraocu- strongly motivate the clinician to perform a lar im~Iant.~~~-l~'Unfortunately, postopera- careful evaluation before initiating the proce- tive inflammation and difficulty in the control of dure. The use of corneal topography imaging glaucoma that often precedes the surgery re- has shown considerable promise in distinguish- main the major obstacles to the use of these ing regular astigmatism from the corneal changes lenses. Posterior chamber intraocular lenses associated with early or mild keratoconus.125-128 have been successfully implanted in patients with oculocutaneous albinism,138but there have Glaucoma been no reports of using the intraocular lens Glaucoma, whether congenital, juvenile, or with the artificial diaphragm for these patients. late-onset, has a strong genetic basis. In addi- Future work may provide surgical strategies tion to the primary glaucoma, there are a that will effectively address the symptomatic number of genetic conditions that are strongly and cosmetic problems associated with mal- predisposed to the development of glaucoma. development. In most instances, the management of glaucoma associated with genetic disorders is essentially Cataract Surgery unchanged from that of classical primary open- Congenital cataracts. Like strabismus sur- angle glaucoma. As noted above, the control of gery, the indications and surgical approaches glaucoma is essential for the successful outcome for congenital cataracts are beyond the scope of of other ocular surgical procedures such as this review. Although it is generally preferable corneal transplants and vitreoretinal surgery. to recognize congenital cataracts as early as

The major potential impact of genetics on the possible to avoid amblyopia, there is evidence management of glaucoma is in the early recogni- that even surgery later in childhood can be tion of the disease in at-risk individuals and in associated with good visual outcomes.3 Glau- the family members. The awareness that glau- coma is a relatively frequent of coma is a major feature of disorders such as congenital cataract surgery, affecting up to 24% Down's ~yndrome,I*~-'~'Weill-Marchesani syn- of operated eyes139for more than a decade after drome,132and aniridia133can guide the clinician the time of surgery.140Certain types of congeni- to more effective screening among a high-risk tal cataracts and those associated with other population. Despite the coexistence of corneal intraocular malformations, such as persistent opacities and glaucoma in Peters anomaly and hyperplastic primary vitreous, are particularly Reigers syndrome, there are reports of success- challenging for the ophthalmic surgeon. Ante- ful surgery when the intraocular pressures are rior lenticonus is frequently associated with controlled.l 13,114.1 Ih,l18.119 Alport's syndrornel4' but is readily recogniz- able. In contrast, the ectasia associated with the iris posterior capsule in posterior lenticonus can Primary repair of iris anomalies is rarely create significant surgical problems if this type undertaken. Most genetic disorders affecting of cataract is not detected or suspected before the iris also cause abnormalities in the rest of surgery. Posterior lenticonus has been observed the anterior segment, leading to glaucoma, sporadically, in familial form^,'^*-^^^ and in asso- cataracts, and corneal opacities. These are the ciation with X-linked Alport's syndrome.142The primary complications addressed by the ophthal- examination of family members may be helpful mic surgeon. For patients with aniridia and in recognizing this condition in a child with a ocular albinism, contact lenses with artificial congenital cataract. Ultrasonography should be diaphragms are available that can provide refrac- seriously considered if the lens is too opaque for tive correction, cosmetic improvement, and some a complete examination of the posterior aspect relief from phot~phobia.~~~However, in many of the lens, the vitreous, and the . 308 MICHAEL B. GORIN

Ectopic lenses. The major causes of atrau- prophylactic peripheral photocoagulation to pre- matic are Marfan's syndrome, vent progressive homocystinuria, and Weill-Marchesani syn- Familial exudative retinopathy, whether of drome. Each of these conditions has significant the x-linked or autosomal dominant type, bears systemic consequences and ocular problems. striking similarities to retinopathy of prematu- Given that many of these patients first come to rity. The management of these eyes parallels the attention of the ophthalmologist, it is essen- that of retinopathy of prematurity.ls6-lSy tial that the underlying diagnosis is established. Finally, one must consider localized abnor- The ophthalmologist is responsible for address- malities of the retina and/or that con- ing visual rehabilitation and safeguarding the tribute to or vision loss. eye from glaucoma and retinal detachment. Retinal angiomas secondary to von Hippel Achieving an unobstructed visual axis can be Lindau disease are frequently the earliest mani- accomplished by either YAG zonulysi~'~~and/or festations of this multisystem disorder that in- lens remo~al.I~~-~~~The long-term safety of pro- cludes CNS hemangiomas, renal cell carcinoma, moting lens dislocation by zonulysis has not and pheochromocytoma. Laser and cryosurgery been established. Other aspects of these disor- have been used for the ablation of these lesions ders must not be overlooked. Marfans syn- and vitreoretinal surgery has been used when drome is associated with significant cardiac chronic exudative or rhegmatogenous retinal abnormalities. Cardiovascular assessment should detachments occur. The treatment of peripapil- be undertaken before surgery to avoid situa- lary angiomas has been generally disappointing. tions in which local anesthesia might be proar- Some investigators report that the natural his- rythmic. Homocystinuria carries a serious risk tory of the condition is better than the results of of thromboembolic events and adequate precau- laser photocoagulation. Peripheral lesions can tions must be taken.lsOJslFinally, Weil Marche- be successfully treated, especially when the sani patients have major ocular abnormalities in

angiomas are small. Careful, regular surveil- addition to ectopia lentis, and nearly 100% of lance and treatment of small lesions can greatly these patients will develop glaucoma.132The reduce the morbidity of this disease.160 high incidence of narrow-angle glaucoma in Other genetic conditions that also contribute these individuals has led some to recommend to retinal detachment or damage include sickle- that prophylactic treatment be considered for cell retin~pathy~J"l-I~~and the Coat's response narrow angles before cataract surgery. observed in some patients with pigmen- tosa.16sJhbEarly recognition of these disorders Retina Surgery and Laser in at-risk individuals can have a significant Retinal detachment remains a major cause of impact on the efficacy of treatment and avoid- visual loss for a large set of vitreoretinal genetic ance of severe complications. disorders. Pathological myopia and lattice degen- Subretinal neovascular membranes can arise eration are relatively common disorders for from such as those associated which autosomal dominant inheritance has been with pseudoxanthoma elasticum or from other reported. Stickler's syndrome and Wagner syn- genetic di~orders,~~~~~~~macular dystrophies, lac- drome are associated with vitreous abnormali- quer cracks associated with pathological myo- ties and a high incidence of retinal detach- pia, and age-related . It is ments. The surgical management of serious unclear if treatment of choroidal neovascular retinal detachments from optic pits and optic membranes arising from different underlying nerve coIobomasIs2 and retinal detachments in genetic disorders has success rates that are conjunction with choroidal colobomasls3 have comparable to the treatment of lesions associ- been discussed. Progressive peripheral retinos- ated with presumed ocular histoplasmosis syn- chisis and outer-layer retinal detachments have drome (POHS) or classic age-related maculopa- been a source of concern for patients with thy. With the recent interest in the use of laser x-linked retir~oschisis.~~~Despite the fact that photocoagulation to promote resorption of dru- most patients with x-linked remain sen lhY and the possibility that such treatment stable, at least one investigator has advocated may reduce the incidence of subretinal neovas- THE INTERPLAY OF GENETICS AND SURGERY 309

cular membranes, there may be a major indica- general anesthesia and may require additional tion for the early recognition and management precautions at the time of s~rgery.'~~J~~Corneal of age-related before the onset of sensation is an important attribute for normal visual loss. By appreciating the familial nature healing after ophthalmic surgery and, although of age-related maculopathy, the clinician can rare, hereditary disorders affecting corneal in- extend the recognition of an affected individual nervation have been de~cribed.~~,'~~-~~' to other at-risk members within a family. Coagulopathies and Vascular Disease GENETIC ASPECTS OF OCULAR SURGERY Although much of ophthalmic surgery in- Anesthesia volves only minimal blood loss, bleeding disor- The transition of ophthalmic surgery from ders, whether genetic or drug-induced, consti- general to local or regional anesthesia and tute a major risk factor. Patients with serious topical anesthesia has had an enormous impact bleeding disorders such as von Willebrands on the safety of ophthalmic surgery. However, disease or hemophilia are generally aware of the majority of pediatric ophthalmic surgery these problems before surgery. However, some continues to require general anesthesia and bleeding disorders are more subtle and patients there are still indications for adults to have need to be specifically asked if they have experi- general anesthesia while undergoing ocular sur- enced specific episodes of bleeding in associa- gery. Because of the potential fatal complica- tion with injuries or previous surgery. The tions of malignant hyperthermia, most surgeons Bernard-Soulier syndrome is associated with and anesthesiologists are aware of this condi- abnormal platelet aggregation, which may be tion. Unfortunately, family histories are often exacerbated by halothane anesthesia.lq2 Dysfi- incomplete and patients at risk for this condi- brinogenemia has recently been identified as a tion may have previously undergone general cause of abnormal bleeding and poor wound anesthesia without diffic~lty.'~~-'~*As noted pre- healing.ly3Individuals harboring the sickle trait viously, some myotonias are associated with an may have relatively normal bleeding times but increased risk of malignant hyperthermia and the increased risk of glaucoma from hyphemas can serve to alert the clinician. A number of is significant.* cases of anesthetic management of hyperkalemic periodic paralysis have been de~cribed.'~~-'~~Wound Healing More importantly, the clinician whose patient Wound healing is a critical aspect of ocular has developed malignant hyperthermia should surgery whether or not tissues are cut with a properly inform the patient and arrange for the blade, ablated, disrupted, or burned by a laser. family members to be evaluated and counseled. Much of our postoperative therapy is directed Studies in mice and drosophila have shown toward controlling the rate of the healing and genetic differences in the susceptibility to inha- inflammatory processes to achieve predictable lation ane~thetics.'~~.~~~It is reasonable to ex- surgical results. Inadequate wound healing can pect that individuals may show wide variations contribute to persistent corneal epithelial de- in requirements and responses for different fects, wound leaks, ocular hypotony, and infec- doses of anesthetics. Halothane hepatitis has tion. Excessive wound healing can result in been described in families17yand special precau- corneal scarring and haze, failure of filtering tions for general anesthesia have been advised blebs from glaucoma surgery, and proliferative for a number of specific genetic disorders includ- vitreoretinopathy. A number of genetic condi- ing prolonged QT syndrome,18ny181por- tions are associated with alterations in wound phyria,182J83hereditary angioneurotic edema,184 healing, particularly those that involve connec- homo~ystinuria,'~~'~~~~~~~~and thalessemia.lXh tive tissue. Some disorders, such as osteogenita Other neurological conditions, such as familial imperfecta and several types of Ehlers Danlos, dysautonomia, and related syndromes, such as are associated with poor wound healing, whereas Biemond's syndrome, familial analgesia and others, such as Rubinstein Taybi syndrome and congenital sensory neuropathy with anhidrosis, pseudoxanthoma elasticum, are associated with can also contribute to unstable responses to hyperplastic reactions and keloid formation in 310 MICHAEL B. GORlN surgical scars. As much as 3% of cases of keloids albinism may be at a higher risk for light- appear to be familial.194Keloid scar formation induced toxicity (based on light toxicity studies in darkly-pigmented individuals appears to be in normal and albino mice) during cataract more frequent than in fair-skinned ethnic extraction, but they appear to tolerate the groups.19sAn unusual example of altered tissue procedure well.138 healing that was indirectly implicated to a ge- Aniridia is a more extensive disorder than netic disorder was two cases of familial Mediter- simply dysgenesis or incomplete agenesis of the ranean fever whose strabismus surgery was iris. As a result, patients with aniridia can complicated by corneal surface breakdown sec- experience a range of difficulties ranging from ondary to the use of colchicine for the treatment persistent epithelial defects after combined kera- of the underlying genetic condition.lYh toplasty and cataract surgery,120,208high failure rate after standard glaucoma filtering proce- Ophthalmic Genetic Disorders That May Affect and problems with control of intraocu- Routine Ocular Surgery lar pressure after cataract s~rgery.'~~-l~' In the previous discussion, I have already Despite reports of complications after cata- mentioned the impact of a number of genetic ract extractions in patients with iris and choroi- disorders on refractive surgery (ie, keratoconus) dal , more recent experience with and cataract surgery (ie, syndromes associated extracapsular methods has been fairly success- with ectopia lentis, aniridia, and posterior lenti- fu1.20y~2'oCataract surgery in patients with conus). However, one must often consider the Down's syndrome and Marfan's syndrome can implications of performing ocular surgery in the also be complicated by postoperative glaucoma face of pre-existing genetic abnormalities of the and retinal detachment. It is important to recog- eye. There is surprisingly little information re- nize that the complications from cataract sur- garding the outcomes for cataract surgery for gery may occur in Marfan's patients who have patients with hereditary retinal degenerations, no evidence of lens dislocation. If the syndrome aniridia, Down's syndrome, and other disorders is suspected based on nonophthalmic features in comparison with uncomplicated surgery. Tim- or a family history, then the ophthalmologist ing of cataract surgery for patients with retinitis must be prepared to deal with zonular fragility pigmentosa can be difficult because of the and an increased risk of anterior vitreous pro- combined mechanisms of visual loss and the lapse at the time of surgery. patient's perception about when cataract sur- gery is indicated.I9' Cataract extraction with CO NC LUSl0 N AN D R ECO MM E N D AT1 0 N S intraocular lens placement is generally success- For the busy clinician, it is difficult to take a ful for patients with .'yx8-200 complete genetic history that might uncover a Some clinicians have expressed concerns that significant hereditary condition. Most individu- operative light exposure be kept to a minimum als have limited awareness or accuracy of ge- and that every effort be taken to minimize the netic disorders in family members beyond first- risk of cystoid , which often degree relatives. This is especially true when the occurs in these individuals independently of conditions may be subtle or obscure. The oph- cataract surgery. Prophylaxis for cystoid macu- thalmologist who is contemplating routine ocu- lar edema has been but its lar surgery can consider a simplified approach efficacy for patients with retinal degenerations based on our knowledge of ocular disease, remains in doubt. One study2ohsuggested that physiology, and genetics. The physician can ask ultraviolet (UV) protective intraocular lenses a limited set of pertinent questions that include (IOLs) might be beneficial in reducing the the patient and their first-degree relatives. In incidence of cystoid macular edema in routine some cases it may be worthwhile to have a patients, whereas a later study2()'failed to con- prepared written questionnaire so that the indi- firm a benefit. Given the equivalent safety of vidual can contact family members and obtain IOLs with UV blocking agents, most surgeons more complete histories. The clinician should will use these lenses in patients with retinal be aware that family histories without clinical degenerations. Patients with oculocutaneous verification serve only as potential indicators of THE INTERPLAY OF GENETICS AND SURGERY 31 1

Table 2. Guidelines for the Clinician factors affecting ophthalmic surgery also high- Patient examination: lights the need for the clinician to completely Ocular abnormalities examine the eye and to be aware of the systemic Corneal sensation, abnormal lid closure, high myopia, features of genetic disorders. The clinician who extensive lattice degeneration. For refractive surgery, one may wish to consider the evaluation of corneal can appropriately suspect Marfan’s syndrome in topography if there is more than minimal astigmatism. a patient with cataracts who does not have lens Systemic abnormalities suggestive of a genetic disorder dislocations, detect occult keratoconus before Body shape, joint deformities, distinctive facies, skin or refractive surgery, or anticipate the develop- teeth abnormalities, unusual scarring ment of malignant hyperthermia during general Patient history Known genetic conditions of any type and complete anesthesia is not only more effectively serving ocular history the interests of the patient but working toward Previous history of surgery and (if appropriate) general ensuring surgical success. anesthesia Continued studies of both rare and common If yes: Specific complications with local or general anes- inherited disorders will lead to a better under- thesia, surgery, wound healing after surgery or an injury, pain management standing of the causes of and offer History of bleeding problems, sickle cell trait or disease, the physician the information with which to excessive joint laxity, muscle weakness, or congenital better optimize and individualize patient care. heart problems. The appreciation of the multifaceted compo- Family history (at least all first-degree relatives: parents, sib- nents of genetic diseases can allow the surgeon lings, children) Eye conditions that were not corrected by glasses or that to anticipate potential problems and perhaps required surgery, especially glaucoma, cataracts at an use prophylactic measures that will lessen the early age, high myopia, macular degeneration, stra- risk of vision loss. A number of the genetic bismus conditions that have been mentioned in this Known genetic conditions of any type, cause of death History of bleeding problems, sickle cell trait or disease, review strongly predispose individuals to cor- excessive joint laxity, muscle weakness, or congenital neal clouding, glaucoma, or retinal detachment.

heart problems. In some of these cases, prophylactic treatments Previous history of surgery and (if appropriate) general (such as scleral buckling for Stickler’s, periph- anesthesia eral photocoagulation for x-linked retinoschisis, If yes: Specific complications with local or general anes- thesia, surgery, wound healing after surgery or an peripheral iridotomy for Weil-Marchesani, and injury, pain management cysteamine drops for nephropathic cystinosis) have been proposed and tested. As more treat- ments are developed and tested for conditions genetic issues. In Table 2, a strategy for a such as glaucoma and age-related macular de- genetically based examination and medical his- generation, we will need to increasingly call on tory is provided. This guideline incorporates the genetics to identify those individuals who are at principles illustrated by the genetic conditions risk for disease. We can use our knowledge of that have been discussed previously. 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