ACUTE HYDROPS IN THE CORNEAL ECTASIAS: ASSOCIATED FACTORS AND OUTCOMES* BY Sanjeev Grewal, MD (BY INVITATION), Peter R. Laibson, MD, Elisabeth J.Cohen, MD (BY INVITATION), AND Christopher J. Rapuano, MD (BY INVITATION)

ABSTRACT Purpose: To identify factors associated with the development of hydrops and affecting its clinical outcome. Methods: Chart review of all patients with acute hydrops seen by a refer- ral cornea service during a 2.5-year period between June 1996 and December 1998. Results: Twenty-one patients (22 eyes) with acute hydrops were seen. Nineteen patients had keratoconus, 2 had pellucid marginal degeneration, and 1 had keratoglobus. Twenty-one of 22 (95%) eyes had seasonal aller- gies and 20 of 22 (91%) eyes had allergy-associated eye-rubbing behavior. Six of 22 (27%) had a diagnosis of Down's syndrome. Six patients were able to identify a traumatic inciting event: vigorous eye rubbing in 4 and traumatic contact lens insertion in 2. The affected area ranged from 7% to 100% of the corneal surface area and was related to disease duration and final visual acuity. Proximity of the area of edemla to the corneal limbus ranged from 0 to 2.3 mm and was also related to prognosis. Three serious complications were observed: a leak, an infectious keratitis, and an infectious keratitis and coincidental neovas- cular glaucomia. Various medical therapies did not differ significantly in their effect on outcome, and ultimuately 4 (18%) of 22 patients underwent penetrating keratoplasty. Best-corrected visual acuity was equal to or better than pre- hydrops visual acuity in 5 of the 6 patients in whom prehydrops visual acu- ity was known, without corneal transplantation. Concltsions: Allergy and eye-rubbing appear to be important risk factors

'Froim the Cornea Sernice, \ills Eve ilospital, Philadelphia.

TR. Am. OPIirii. SoC. VOL. XCVII, 1999 188 Grewal in the development of hydrops. Visual results are acceptable in some patients without surgery. Close observation allows for the early detection and treatment of complications such as perforation and infection.

INTRODUCTION Acute hydrops is the development of marked edema of the corneal stroma and epithelium following a break in Descemet's membrane (Fig 1). It is well known to occur in keratoconus and has also been reported in other

_~~ ~ ~~~~~~~~~~~~~~~

5.. FIGURE 1 Severe corneal lhydrops in patient withi keratoconns. corneal ectasias, specifically, pellucid marginal degeneration and ker- atoglobus." Clinically, it occurs in 2.6% to 2.8% of patients wth kerato- conus.'" Patients typically report acute onset of blurred vision, ocular irri- tation or pain, tearing, and photophobia, and they frequently notice a corneal opacity that can be apparent to the unaided eye. The usual clini- cal course is one of slow improvement, with corneal scarring and flatten- ing. Recently, one study has shown that nearly 60% of patients ultimately require penetrating keratoplasty for visual rehabilitation.' Rarely, serious complications, including corneal perforation (Fig 2), microbial keratitis, and glaucoma, have been reported. 1,4-7 The purpose of this study was to examine factors associated with the development of hydrops in a group of patients with corneal ectasia.

METHODS

The clinical records of all cases of acute hydrops seen by the Cornea Service at Wills Eye Hospital, Philadelphia, between June 1996 and Acute Hydrnps in the Cor-neal Ectasias1 189

FIGURE 2 Aquieous leak anid flat aniterior chamiiber vith hyd(rops.

December 1998 were reviewed retrospectively. Ocular and systemic fac- tors possibly predisposing patients to the development of hydrops were recorded and analyzed, including the presence of allergies, eye rubbing, and Downis syndrome. All patients had detailed ocular and systemic his- tories recorded at their initial visit and had thorough slit-lamp evaluations at initial and follow-up visits. Detailed, systematic corneal drawings were made at all visits by the examining physician.' If the exact dimensions of the edematous area were not indicated on the drawings, they were meas- ured fromn the scale drawings to allow for calculation of the affected area and proximity to the corneoscleral limbuis. When required, additional information was obtained from the patients by telephone interview.

RESULTS During the stuidy period, 26 cases of acute corneal hydrops were seen. Four cases were excluded from the study because hydrops had been pres- ent for more than 2 weeks prior to initial assessment, thus precluding accurate assessment of the initially involved area. The details of the remlaining 22 cases are summarized in Tables I through VI. The age of patients at the onset of hydrops ranged from 12 to 66 years, with a mean of 39.3 years. The male-femlale ratio was 13:9. One patient (cases 16a and b) had simultaneouis bilateral involvement. In 19 cases, the eyes had pre- existing keratoconuis; 2 had pellucid mar-ginal degeneration and 1 had ker- atoglobus. In 20 cases (91%), a history of seasonal allergy with eye-rub- bing behavior was given by the patient or primary caregiver. In oIne case, allergy was denied but eye-rubbing behavior was present, and in another case, allergy was present but eye-rubbing behavior was denied. Only 6 patients (27%) felt that they could identify an inciting event: 4 patients 190 Grewal

TABLE I: PATIENT DEMOGRAPHICS

CASE AGE SEX EYE DOM HAND ECTASIA

1 12 M L R Keratoconus 2 51 M L R Keratoconus 3 43 F L R Keratocontis 4 44 F L R Pellucid 5 29 M L R Keratoconuis 6 56 M R L Keratoconus 7 20 M R R Keratoconuis 8 45 M R R Keratoconus 9 35 F R R Keratoconus 10 18 F L R Keratoconus 11 49 M R R Pelluicid 12 43 M L R Kercatoconus 13 44 M L R Keratoconus 14 27 F R L Keratoconus 15 23 M L R Keratoconus 1 6a 59 M L R Keratoconus 16b 59 M R R Keratoconus 17 38 F L R Keratoglobus 18 66 M R R Keratocontis 19 25 F L R Keratoconuts 20 46 F R R Keratoconius 21 32 F R R Keratocontis reported vigorous eye rubbing, and 2 patients reported traumatic contact lens insertion immediately preceding the onset of symptoms. Six cases (27%) occurred in patients with Down's syndrome The area of corneal involvement ranged from 7% to 100% of the total corneal surface area as calculated from detailed corneal drawings. Larger areas of involvement were associated with slower recovery (p = 0.49, II = .02) and worse final visual acuity (p = .51, fl= .02). The proximity of the edema to the corneoscleral limbus ranged from 0 to 2.3 mm, and conti- guity with the limbus was associated with slower resolution (r = -0.42, H1= .05) and poorer final acuity (p = -0.38, H = .01). Associations were deter- mined using Pearson correlations. Treatment methods varied case by case and included topical hyper- tonic agents, corticosteroids, antibiotics, cycloplegics, and topical and sys- temic ocular hypotensive agents. Different medical treatments did not result in significantly different visual outcomes or duration of disease. The mean duration of hydrops was 16.3 weeks, with a range of 5 to 36 weeks. During the course of hydrops, 3 eyes (14%) developed serious ocular complications: bacterial keratitis (case 1), aqueous leak and flat chamber (case 8), and bacterial keratitis (case 12); in case 12, neovascular Acute Hydrops in the Corneal Ectasias 191

TABLE II: PREDISPOSING FACTORS

CASE ALLERGY EYE RUBBING DOWN'S INCITING HISTORY SYNDROME EVENT

1 Y Y N None 2 Y Y N CL insertion 3 Y Y N None 4 Y Y N None 5 Y Y N None 6 Y Y N None Y Y N None 8 Y N Y CL insertion 9 y y Y None 10 Y Y N None 11 N Y N None 12 Y Y Y Nonie 13 Y Y Y Nonie 14 Y Y Y Rubbing 15 Y Y Y None 16a Y Y N Rubbing 1 6b Y Y N Rubbing 17 Y Y N Rubbing 18 Y Y N None 19 Y Y N None 20 Y Y N None 21 Y Y Y None

CL, conitact lenls. glaucoma was coindicentally discovered on initial examination. All com- plications were managed medically, without surgical intervention. Penetrating keratoplasty was performed on 4 eyes (18%) during the study period (cases 4, 9, 16, and 20) for visual rehabilitation, and no episodes of rejection were observed during follow-up. All surgeries were performed on eyes after stabilization of ocular conditions with medical therapy.

CASE HISTORIES Following are selected case histories: Case 1 A 12-year-old boy was referred for assessment of acute corneal hydrops after recent diagnosis in another country. On initial assessment, he had markedly reduced visual acuity in his left eye, intense photophobia, and pain. His previous ophthalmologist gave a history of vernal conjunctivitis, and the patient admitted to eye rubbing. Initial treatment included topi- 192 Grewual

TABLE III: SIZE OF EDENIATOUS AREA AND OUTCONIE

AFFECTED AREA CASES TINIE TO FINAL V7ISUAL (%) RESOLUTION ACUITY

1-25 16 20/50 8 5 20/80 1() 14 20/30 11 16 2(/30 12 / (CF° 161b 19 20/200 19 6 20/10(0

26-50 4 16 20/50 5 8 CF 6 32 20/200 28 20/80 13 16 Cannot assess' 15 30 (,F° 16a 20 20/200 2() 16 20/100

51-75 1 10 20/200 :3 11 2(0/200 9 20 20/200* 21 8 20/4()

76-100 14 24 C,F° 1 7 36 IIM 18 28 CF

'Acuity limited owing to severe retardation. cal hypertonic therapy, prednisolone acetate, cyclopentolate, and lev- obunolol. He had weekly follow-np examinationis, and during the seconi( one, a large comeal infiltrate was observed centrally (Fig 3). Corneal cul- tures were taken, and the patient was admitted to the hospital for treat- ment with fortified topical cefazolin and tobramneycin therapy given every hour. Cultures revealed streptococcal bacterial infection. Over the next several weeks, the infiltrate resolved with scarring and resolution of the corneal edema (Fig 4). By the 10th week, visual acuity had retuirned to 20/200, the level that it had been prehydrops.

Case 10 An 18-year-old womani with known keratoconus and rigid gas permeable contact lens wear, and with visual a visuial acuity of 20/5() due to scarring, Acute Hydrops in the Corneal Ectasias 193

FIGURE 3 Bacterial keratitis (case 1).

TABLE IV: PROXIMITY TO LIMBUS AND OUTCOME

DISTANCE TO CASE TIME TO FINAL VISUAL LIMBUS RESOLUTION (WK) ACUITY

0 mm111 I1 10 20/200 14 24 CF° 16a 20 2(/200 17 36 HM

0.1 - 1.0 mm11 6 :32 20/200 9 20 20/200* 18 28 CF 21 8 20/40

1.1 - 2.0 mm 2 16 250/o 3 11 20/200 4 16 20/50 5 8 CF 7 28 20/80 10 14 20/30 1l1 16 20/30 12 7 CF° 15 30 CF* 16b 19 20/200 19 6 20/100 20 16 20/100*

2.0+ mm 8 5 20/80 13 16 Canniot assess'

'Acluitv limite(I oNwinig to severe retardationi. 194 Grewal

FIGURE 4 Resoluition with miedical therapy alone (case 1).

TABLE V: TREATMENT AND OUTCOME

CASE INITIAL TINIE TO (WE) VISUAL ACUITY TREATMENT RESOLUTION

1 aq,cyc,hyp,ster 10 20/200 2 hyper 16 20/50 3 ahx,cyc,hyper 11 20/200 4 aq,hyp 16 20/50 5 abx, aq, cyc 8 C,F 6 abx, aq, cvc 32 20/200 I aq, hyp, ster 28 20/80 8 aq 5 20/80 9 abx, hvp, ster 20 20/200( 10 alx, a(q 14 20/30 11 aq, hyp 16 20/30 12 alhx, aq, eye I CF* 13 abx, cyc, hyp 16 Canniiot assess' 14 abx, eye 24 CF* 15 eye,hyp, ster 30 C'F 16a abx 20 2(/200 16b abx 19 20/200 17 aq, hyp, ster 36 HM 18 abx,hyp,ster 28 CF 19 aq,hyp 6 20/100 20 hyp 16 20/100* 21 hyp 8 20/40 abx, antibiotic; aq, aqueous suppressants; cyc, cycloplegic; hyp, hypertonic; ster, steroid. Actuity limite(d owing to severe retardation. Aciute Hydirops in the Corneal Ectasias 195

TABLE 'I: VISUAL ACUITY BEFORE AND AFTER HYDROPS

CASE PREHYDROPS VA POSTHYDROPS VA

1 20/200 20/200 4 20/60 20/500 6 20/80 20/200 9 20/200f 20/200f 10 20/50 20(/30 1 1 20/30 20/30 21 CF 20/40 'After surgerv. fAcuit7 lillite(l ow\\illg to severe rettr(lIttioio. presented with a 2-day history of a "bluie" left cornea, pain, and decreased vision. She had a history of seasonal allergy and eye-rubbing behavior. Acute corneal hydrops was diagnosed, and the patient was started on top- ical erythroinycin ointment. One month later, the hydrops had worsened, and topical levobunolol was added, along with topical hypertonic drops. At 6 weeks, topical prednisolone acetate was added for developing corneal neovascularization. The edema began to improve, and by 10 weeks the edema had suibstantially resolved. Best-corrected acuity was 20/30, which exceeded prehydrops acuity by two full lines. Case.s 16a and b A 59-year-old man with seasonal allergies presented with a week's history of a "film" over his left eye. He admitted to vigorously rubbing his eyes several times a day with a handkerchief, as he had done just prior to the onset ofhis symptoms. A diagnosis ofbilateral hydrops was made, with the left eye muich more severely affected than the right. Treatment with top- ical erythromiycin ointment was started. Over the next 12 weeks, the edema graduially improved in his right eye, with no significant improve- ment in visual acuity. A localized area of edema persisted in the left cornea for 20 weeks, at whiclh time a decision was made to offer the patient penetrating keratoplasty to allow for visual rehabilitation. On the most recent follow-up visit, the suibjective quiality of vision had improved sub- stantially in his left eye after surgery, althouigh acuity remained 20/200 in the early postoperative period.

DISCUSSION Acute hydrops has been associated in the past with chronic allergy. A British study of corneal hydrops in a contact lens department patient 196 Grewa^l population showed that hydrops developed at a greater rate in keratoconus patients with severe allergic disease than in patients with little or no aller- gy.' Hydrops has also been reported as the presenting sign of keratoconuis in children with severe atopic or vernal disease." The incidence of kerato- conus in children with allergic disease has been fonind to be 7%, of which 20% developed hydrops in one study."' The present stuidy shows that allergy existed clinically in 21 of 22 cases (95%), and associated eye-rub- bing behavior was present in 20 cases (91%). Eye rubbing has been pre- viously suispected to worsen keratoconuis, althouigh the exact mechanism remains unknown." In this study, 14 of 22 cases (64%) had an association of opposite dominant hand and affected eye; this association may suggest a more traumatic type of' eye rnibbing across the face. Six of22 cases (27%) were able to identify a single trauimatic inciting event: rubbing or digital self-trauma in 4 and contact lens insertion in 2. This reinforces the role of trauma in the development of hydrops aind the importance of prevention of trauma by treating irritating ocular conditions such as allergy anld ble- pharitis aggressively to reduce the urge to rub. In our stuidy, 6 of 22 (27%) of the hydrops cases occurred in patients with Down's syndrome. This rate is much higher than in a British study,' which reported 2 of 147 (1.4%). The difference may be due to a selection bias, in that the population that was studied in the United Kingdom was a contact lens-wearing poptulation, which is less likely to have patients with mental retardation, as opposed to the popuilation we studied, which was a corneal referral patient population. Patients with Down's syndrome tend to rub their eyes to relieve itching, thus stimulating phosphenes in eyes with poor vision," and they are less likely to stop eye rubbing when instructed. This again emphasizes the significance of trauma in the devel- opment of hydrops. The burden of hydrops in these patients is staggering: 29% of blindness in Down's syndrome patients has previously been attrib- uted to hydrops.'2 The size and location of the edematouis area of cornea did affect the final visual acuity and time to resolution, with larger affected areas and close proximity to the limbus having poorer visual acuity after resolution and requiring longer time to resolution The course is unpredictable until closure of breaks in Descemet's membrane occurs, at which point resolu- tion progresses more rapidly. The duration of disease is highly variable, with time to resolution of edema in this series ranging from 5 to 36 weeks with a mean of 16.3 weeks. This length of time is in agreement with other studies, whielh report improvement over 2 to 4 months." All of the patients in our stutdy who ultimately had equal or better visual acuity after resolution of the hydrops Acuite Hydrops in the Corneal Ecta.sia.s 197 (without surgery) lhad resolution in 16 weeks or less. Medical therapy varied greatly and ranged from 1 to 12 different med- icines over the couirse of treatment. No single medication or medication combination was found to have a significant impact on the duration of dis- ease or visual outcome. Interestingly, no patient treated with topical antibiotic drops or ointmnent developed infectious keratitis as a complica- tion of the hydrops, and neither of the 2 patients who did develop corneal uilcers was on prophylactic topical antibiotic therapy. Risk factors for infection may include epitlhelial defects from ruptured bullae, and infec- tion may progress rapidly owing to the existence of intrastromal fluiid clefts, which could theoretically allow for easier passage of organisms into the corniea.4 Conformuational clhanges in the uisuially highly organized col- lagen lamellae of the cornea may also ease the spread of organisms.5 Serious complications (infectious keratitis, perforation, glaucoma) occurred in 3 of 22 (14%) of patients while under observation. This rate was significantly higher than that reported in a British study (2 of 147 [1.4%]).' Frequent follow-up examinations (initially weekly) allowed for early diagnosis and intervention in these 3 cases, and no eye was lost as a result. During the study period, only 4 of 22 (18%) of the affected eyes underwent surgery. This rate is much lower than in other studies, most likely because of the short observation period: The mean time to trans- plant has been previously reported to be between 1.3 and 2.3 years.' Final visual acuity in 5 ofthe 6 patients with known prehydrops vision was equal or better without surgical intervention; this suggests that good visual out- comes often can be achieved witlhouit surgery.

CONCLUSIONS The clinical diagniosis of acute corneal hydrops is easily made with the dramatic slit-lamp biomicroscopic findings and appropriate clinical histo- ry. The management of the disease is primarily by observation with topi- cal medical therapy aimed at relieving symptoms and expediting the res- olution of corneal edema. Good visual results can often be obtained with- out surgical intervention. Serious complications can occur and should be managed promptly with appropriate diagnostic and therapeutic interven- tions. It may be possible to reduce the burden of morbidity by prevention, with patient education about the importance of avoiding ocuilar traiuma, and by medical therapies aimed at reducing the irritative symptoms of conditions such a.s allergies and blepharitis. Once hydrops develops, top- ical antibiotic ointment mnay be helpful in decreasing surface breakdown and preventing superinfection. 198 Grewal

REFERENCES

1. Tuift SJ, Gregory WM, Buckley RJ. Actute corneal hydrops in keratouonus. Ophlthlalmtiology 1994;101:1738-1744. 2. Carter JB, Jones DB, XVilhlelmuitis KR. Actute hy(lrops in pelltuci(l malrgilnal corleal degeueratioui. Am]J Ophthalniol 1989;107:167-17(). 3. Amsler MM. Quelques donniiees du probleme dti keratcone. Biull Soc Bel(le Opltahnol 1961;128:331-354. 4. Feder RS, Wilhelmus KR, Vloil SD, et al. Initrastromiial Clefts in keratoconus patienits wvith hydrops. An7 J Opithanliol 1998;126(1):9-16. 5. Donnenfel(d ED, Schrier A, Perry, lID, et al. Inifectious keratitis Nwith corneal perforation associated with cornieal hvdrops ai(l conitact lenis wear in keratoconus. BrJ Ophthalomol 1996;80:409-412. 6. Rowsoni NJ, Dart JK, Btuckley RJ. Corneal neovascularization in atcuite hvdrops. Eye 1992;6:404-406. 7. RuibsaImen1 PE, McLeish NN'NI. Keratoconius Nwitlh acuite lhvdrops and perforatioll. Cornea 1991;10(1):83-84. 8. 'Waring GO, Laibson PR. A systemiiatic method of (draNing corneal pathologic cond(1i- tions. Arcl Ophthalozool 1977;95:1540-42. 9. Rehalnly U, Remult S. Corneal hydrops associate(l Nwitlh vernal conljunctivitis as a pre- senting sign of keratoconules in children. Ophthalmology 1995; 102:2046-2049. 10. Khani MD, Kundi N, Saeed N, et al. Incidenice of keratoconuis in spring catarrh. BrJ Ophthalmol 1988;72:41-43. 11. Koeniig SB, Smith RWNr Keratoconus and cornieal hydrops associate(I \vith compulsive eve rnhhbing. Refract Coni Stirg 1993;9:383-384. 12. Cullen JF. Blinidness in Monigolismii (Down.s svndromie). Br J Ophithalmol 1968; 66:1137-1143. 13. Camleroni JA, Al-Rajhi AA, Badr IA. Corneal ectasia in vernal keratoconjunctivitis. Ophthalmology 1989;96:1615-1623.

DISCUSSION

DR THOMAS J. LIESEGANG. Hydrops can be the presenting feature of ker- atoconus, especially in patients with Down's syndrome' or vernal conjunc- tivitis.2 Acute hydrops has also been described in mentally retarded patients with allergies and with congenital rubella syndrome.' Eye rub- bing is a feature common to many of these entities.45 This series from Wills Eye Hospital reports hydrops in association with a corneal ectasia. There were 22 eyes in 21 patients with acute hydrops in a recent 2 year period, reflecting a large corneal referral prac- tice. Nineteen eyes had keratoconus, 2 had pellucid marginal degenera- tion, and 1 had keratoglobus. Mean age of onset was 39.3 years. Tuft and associates6 from Moorfields reported a series derived from a contact lens clinic. They identified 147 eyes of 124 patients with acute hydrops from a database of 5,242 eyes with keratoconus, giving an inci- dence of 2.8% over a 7 year period. A prior study by Amsler7 reported an incidence of 2.6%. In the Moorfields study, patients with pellucid mar- ginal degeneration or keratoglobus were excluded. The meian age at onset of hydrops was calculated differently but was approximately 24 years. Acuite Hydrops in the Cornieal Ecta.sia.s 199 Advanced ectasia was detected clinically in both series, with the Moorf'ields stdcly having prehydrops keratometry readinigs to confirm this observation. The Wills series reported a very frequent association with seasonal allergy and eye-rnbbing behavior. Twenty-seven percent had Down's syn- drome, and 27% were able to identify an inciting event, nsnally digital trainma or contact lens insertion. In the Moorfields series, atopic disease was not classified in the same way, althonigh the investigators indicated that it was extremely frequent. There were only 2 patients with Down's syndrome in their contact lens-based stndy. Penetrating keratoplasty was performed in 59% of patients in the Moorfields stndy compared with 18% in the Wills stucly. Prior to 1982, eyes with hydrops at Moorfields were often grafted acutely before resolu- tion of the edema. A stndy from Germany' published in 1979 indicated that the success rate for corneal transplantation performed for acute hydrops is similar to that for simple keratoconus, and this report might have influenced this aggressive treatment of hydrops. The investigators altered their policy during the course of their study and later assessed patients after resolution of the hydrops. The Wills gronp used a more con- servative approach. The Moorfields gronp notedl that the eyes with hydrops had a greater risk of graft rejection. Graft rejection was not a problem in the 4 eyes in the Wills study. Occasionally, the vision may improve to better than the pre-hydrops vision because corneal scarring causes the cone to flatten. Few patients had vision known prior to hydrops in the Wills study, but 6 of 8 had improved vision after the hydrops episode and 4 of 6 withont surgery. This has also been noted in Moorfields stndy as well as several other isolated reports in the literature. In Japan, Sato9 nsed this specific observation to conclude that a controlled posterior radi- al keratotomy would reduce myopia, and it becaame the forernnner of ante- rior radial keratotomy utilized to flatten the corneal cnrvature. In the Wills series, various medical therapies, including topical hyper- tonic solutions, corticosteroids, antibiotics, cycloplegics, and ocnlar hypotensive agents, did not differ significantly in their eff'ect on the ont- come. All snrgeries were performed on eyes stabilized by medical therapy prior to surgery. The follow-np on this study is short, and there are a high nnmber of Down's syndrome patients; both of these factors contribnte to a low rate of corneal transplantation. Other treatment options for acute hydrops reported in the literature include excision of a vertical ellipse of cornea, a conjunctival flap, pressure patching, medical tarsorrhaphy, para- centesis, hyperosmotic agents, chemical or thermal cauterization of the cone, injection of autologous bloodI into the anterior chamber, an(d emer- gency penetrating keratoplasty.6 The Wills stucly did not assess the long- 200JO Gretcal terml sUccess in terms of xisuial acuity. A recuirrence of the hydlrops is unlikely; the corneal ectasia, hoNever, miay continuie, with corneal trans- plantatio)n more likely in the fututre as noted in other, longer-term studies. In the Wills stuidy, three seriouis complications occuirred, incluiding a leak, a leak with microbial keratitis, and a leak with micerobial keratitis and neo- vascular glauicomo-ia. Each of these complicationis has been reported in this setting."'"' Other complications reported in the literatuire incluide perfo- ration, psetidocyst or intrastomlal cleft forimcation, mualignant glaucomal, and corneal neovasctularization.6'''"13 The auithors found a protective effect of prophylactic topical antibiotics in this patient poptulation. Up to 7.9% of patients with Down's syndrome can develop kerato- conus, and almlost 30% of blindlness in Downv's syndrome has been attrib- uted to hvdrops."'95 In Down's syndrome a specific approaclh to hydrops has been ptublished.'6 Patients are placed un(ler general anestlhesia to eval- uate the cornea for a leak aind( a cuiltuire obtained. An injection of corticos- teroid and atntibiotic is delivered subconjunctivally, and botulinulm toxic is injected into the levator palpebrae muscle to induice a therapeutic ptosis. Patients are treated with topical corticosteroids and evaluated uinder anes- thesia at weekly intervals. They are poor can(li(lates for corneal transplan- tation. The Wills study does not contribute to the pathophysiology, since ker- atometry, corneal topography, and monitored corneal biomnicroscopic changes prior to hydrops were not available. Information might have been helpful from the contralateral eye but was not recorded in a systematic fashion. The high incidence of Dowln's synldromne patients leacds to incom- plete data. The Wills series provides a firm basis for espousing a conservative approach to hydrops and abandoning the aggressive approach predomi- nant in the literature. Cycloplegics, dark glasses, contact lens avoidance, prophylactic antibiotics, an(l topical corticosteroids for neovascularization, along with monitoring, can lead to an acceptable short-term outcoome. The long-term visual results are not available.

REFERENCES

1. Valella MT. Keratoconis \with acutite corneal hydrops. J Am,l Optoil Assoc 1989;60:578- 580. 2. Rehanvy U, RIlumlelt S. Cornieal hvdrops associated with verial cnjiinctivitis as a pre- seintinig signi of keratoconuiis in clhildren. Ophthalmolo,y1 1995;102:2046-2()49. :3. Boger W\7P, Petersein RA, Robb RM. Keratoconuis almd atcute hydrops iin menitally retard- e(I paItieiits w\ith conigenital ruhella svindrome. Aumt J Ophlthalmol 1981;91:2:31-233. 4. Koeniig S13, Susiitlh R\V. Keratoconis anid cornea1l hdrops associated( with compulsive eve rulbl)ing. Refrict Conieal Surg, 1993;9:383-384. 5. Gritz D(,, NMeDonniiell PJ. Keratoconus and oculatr massacge. Amil j Oplhthalmol Acuite Hydrops in the Corneal Ectasias2 20

1988; 106:757-758. 6. Tuift Sj, Gregory \VNM, Buckley RJ. Acuite cornieal hvdrops in keratocoiunis. Ophlthlalmology 1994;101:1738-1744. 7. Amiisler MM. Qiellles (louniices (du prohleme dii keratcoine. Biil Soc Belge Ophltalmoi 1961;128:331-354. 8. Alherth B. Therapy of acute keratoconutis. K/itn Alootatsbl Atwgeohilkie 1979;174:466- 470. 9. Sato T. Ueber- cilue Operatiouismetho(le zoir Behlian(Ildilig des Keratokonilis (descemietspaltung). Klit IMotiatsbl Aiweg eilked 1941;107:234-238. 10. Rowson NJ, Dart JK, Buckley RJ. Corneal neovascularisation iu acute hydrops. E,ye 1992;6:404-406. 11. Rubsamen PER MeLeish WVM. Keratoconuiis with lacute hydrops aind perforationi. Brief case report. Cornea 1991;10:83-84. 12. La-houd S, Brownstein S, Laflammiiiie MYr, et al. Keratoconutis with sponitanieouis perfora- tionl of the cornea. Cani J Ophtlialol 1987;22:230-233. 13. Feder RS, \Vrilhelniutis KR, V7oid SD, et al. Initrastromiial clefts in keratoconulis patienlts Nith hydrops. Aoi J Ophlthalintol 1998; 126:9-16. 14. Sluisher MM, Laibson PR, Mulberger RD. Acute keratoconius in Down's syndrome. Ai I Ophithalmol 1968;66:11371-1143. 15. Cuilleni JF. Blind(lness in miionigolismii (Down's Syndrome). Br J Oplthalmoi 1968;66:1137-1 143. 16. Tsaloumilas MD, McDoninlell PJ. The miainaagemilenit of keratoconilis with acuite hydrops in the Down's syndrome and mentally retarded patienit (Letter). Eye 1996;10:644-646. DR WILLIAM M. BOURNE. In some cases, early surgery mLay be indicated. Why is it necessary to wait 7 to 9 months for the cornea to clear when a keratoplasty can give them both relief and good vision? To heal sponta- neously, endothelial cells must grow in from the periphery; a keratoplasty would prevent that and save the peripheral endothelial cells. Early surgery may also prevent vessels form growing in from the periphery. I do not believe that grafting a cornea into a thicker recipient is doomed to failure; we graft many patients with pseudophakic bullous keratopathy who have very thick corneas. These corneas quiickly become thinner as they heal. I wish to congratulate the authors on an excellent paper. DR GEORGE 0. WARING. Serendipity plays an important role in our med- ical advances. Dr Liesegang mentioned the serendipitous observations by Dr Sata that the cornea flattens after acute hydrops in keratoconus. He noted this in approximately 35 cases that he studied very carefully. This led to the posterior keratotomy an(d finally the anterior keratotomy, which is the basis of much of our refractive surgery today. Those of us who are clever enough to make these observations and can think "outside the box" can make significant contributions to our medical knowledge and tech- niques. For instance, acuite hydrops affects only a few people, buit refrac- tive surgery can apply to many individuials. I have two questions. Can you tell me more about the optical outcomes? Did these corneas flatten? Were 202 Gretval aniy of these individuals who( needed contact lenses before the episode of acute bydrops able to get along withouit contact lenses after the acute blydrops? The second question is, How long do you wait? Do you wait for 6 to 9 months, or do you operate sooner? Wbcat are youir criteria for oper- ating sooner? DR MELV'IN L. RUBIN. I tlborouighly enjoyed the paper even thouigh I'm not a corneal specialist. You imentioned that eye rubbing is associated with acuite hydrops; were youi able to correlate which eye was affected with whether the patient was right-handed or left-handed? One might think that if a patient were right-handed, the right eye wouild be more often affected if eve ruibbing were a factor.

DR WILLIAM S. TASNIAN. It seems to mie that I once saw a patient witlh Leber's congenital amaurosis who developedI acute hydrops. Is there an association? DR PETEiR R. LAIBSON. I would like to thcank my discussaints, paiticularly Dr Tom Liesegang, for a kind and thorouglh analysis. To answer Dr Rubin's (uestion, we hcave had no patients with amau- rosis that we can detect in this series. Concerning Dr Rubin's question about haandedness, we were a little suirpiised in that the majority of patients who were right-handed had a higher incidence of hydrops in the left eye. It is hard to rub the left eye with right hand and we can't explain why this discrepancy exists. I still feel that eye rubbing does have an important effect on thinned corneas which may lead to ruipture of Descemet's membrane. A very ilmportant question has been raised by Dr Liesegang and Dr Waring. When should a cornieal transplant be done after a patient has corneal hy(drops? Can the patient wait until the hydrops is resolved? I hcave found that doing a corneal transplant during the hydrops phase of a patient with hydrops the healing process is very irreguilar and hard to predict. Unlike a patient with pseudophakic bullous keratopatlhy, where there are no clefts and cysts in the corneal stroma, there are areas of clefts and cysts whiclh make healing quite irregular. With pseudophakic bullous keratopathy there is usuially uniform thickeninig around the periphery, whereas if' a corneal trainsplant is done for acuite hydrops there is usually one part of the cornea that is markedly edemiiatous and another part that is of' norm-al thickness. It is this discrepancy that we try to avoi(l by doing the corneal transplant after the hydrops has resolved. Another reason to wait for the hydrops to resolve is that many patients have corneal flatteninig ani(d can once again wear a contact lenis, whereas Acsute Hyjdrops in the Corrieal Ectasias 203 they could not before the hydrops and healing has occured. There is certianlv Ino harml in waiting 3 to 4 months to see how the res- oluition of the hydrops goes. In most of ouir cases, the resolution had occured by 4 to 5 months and waiting this long did not jeopardize the patients visUcal accuity. Dr Waring asked the question abouit optimum outcomes after contact lens fitting. A lot of our patients disappear fromii ouir practice after the hydrops is resolved and it is hard for us to determine what percent of patients do well after corneal hydrops healing. Dr Elisabetlh Cohen, our contact lens fitter extraordinaire, finds it sometimes more difficult to fit a cornea after hydrops has resolved becauise of the flattening but it is cer- tainly worthwhile trying to spare the patient the possibility of a corneal transplant. Tom, I want to thank you for your very inclusive and all consuming coimments, using Tuft's paper and our paper side by side. ToIm1 does a fan- tastic job in reviewinig things in multltiple fields in CORNEA and I appre- ciate his commenits.