The Madurai Intraocular Lens Study II: Clinical Outcomes

The Madurai Intraocular Lens Study II: Clinical Outcomes N. VENKATESH PRAJNA, MD, K. S. CHANDRAKANTH, MD, R. KIM, MD, V. NARENDRAN, MD, SELVI SELVAKUMAR, MD, C. ROHINI, MD, N. MANOHARAN, MSc, SHRIKANT I. BANGDIWALA, PHD, LEON B. ELLWEIN, PHD, AND CARL KUPFER, MD To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG). l METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilaterally visionimpaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with followup visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists. l RESULTS: At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evalual

PURPOSE:

Accepted for publication Aug 19, 1997. From the Aravind Eye Hospital and Post-Graduate Institute of Ophthalmology, Madurai, India (Drs Prajna, Chandrakanth, Kim, Narendran, Selvakumar, and Rohini, and Mr Manoharan); University of North Carolina, Chapel Hill, North Carolina (Dr Bangdiwala); and the National Eye Institute, Bethesda, Maryland (Drs Ellwein and Kupfer). Supported in part by the World Health Organization under contract NOl-EY-2103 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland. Reprint requests to Carl Kupfer, MD, National Eye Institute, 3 1 Center Drive, MSC 2510, Bldg 31, Room 6A-03, Bethesda, MD 20892-2510; fax: (301) 496-9970.

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tion time point. Cumulatively, the incidence of serious complications of all types throughout the l-year study period was 14.5% for patients in the ICCEeAG group and 7.7% in the ECCE group (P < .OOl). Best-corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .OOl). l CONCLUSION: Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PCIOL is superior to ICCE-AG in terms of both visual acuity restoration and safety.

C

ATARACT

IS THE

MAIN

CAUSE

OF CURABLE

BLIND-

ness worldwide, with the developing world accounting for approximately three fourths of this blindness in many countries.’ Although extracapsular cataract surgery with posterior chamber intraocular lens (ECCE/PC-IOL) is the treatment of See also

pp.

1-13,

26-35,

and 90-93.

choice for most of the developed countries, intracapsular cataract extraction with aphakic glasses (ICCEAG) will remain common in d.eveloping-country settings.2 Differences in terms of sight restoration and operative safety are not well understood. The Madurai Intraocular Lens Study (MIOLS) was designed with the primary objective of evaluating the visual acuity outcome and complications associated with the use of ECCE/PC-IOL in comparison to the standard method of ICCE-AG.

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METHODS THE MIOLS

STUDY

DESIGN

AND

METHODS

HAVE

ALREADY

been presented. 3 Briefly, the MIOLS was a nonmasked randomized controlled trial of ICCE-AG vs ECCE/PC-IOL add ressing both clinical (safety and efficacy) and nonclinical (visual functioning and quality of life) outcomes. Thirty-four hundred patients, 1,700 in each treatment group, were recruited for surgery at the Aravind Eye Hospital, Madurai, India. Male and female patients between the ages of 40 and 75 years with operable cataract and bestcorrected visual acuity equal to or worse than 20/120 in both eyes were enrolled. One eye per subject was included in the study and followed up for 1 year after surgical intervention. A total of 34,096 patients were screened to enroll the required patient population of 3,400. After obtaining informed consent, the presurgical examination and preparation were identical for all patients. A sealed envelope containing the random treatment assignment was attached to the individual patient data booklet and opened only when the patient was on the operating table. The surgeries were performed by one of four study surgeons, all of whom had recently completed residency training that included a minimum of 100 ICCE surgeries and 50 ECCE surgeries with IOL implantation. All surgeries were performed under local anesthesia with a standard retrobulbar ciliary block and an O’Brien facial block. The ICCE surgery was performed without magnification using an operating light. A limbal-based conjunctival flap was made. After cauterization, a midlimbal partial-thickness groove was created. The anterior chamber was entered by a stab incision, and the cornea1 section was then extended using corneoscleral scissors. One 8-O silk suture was placed through the incision and looped aside. A peripheral iridectomy was performed and the lens delivered using a cryoprobe. The anterior chamber was reformed with air, and the wound was sutured with a minimum of five interrupted 8-O silk sutures. In case of an accidental rupture of the lens capsule, the nucleus was removed with a lens loop and the cortical material was aspirated using a Simcoe cannula. In case of vitreous loss, the vitreous was cleared from the cornea1 section by a wet sponge and the wound was closed. After replacing the conjunctiVOL.

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val flap to its original position, 0.5 ml of subconjunctival gentamicin was injected. The ECCE/PC-IOL surgery was performed using an operating microscope. A fornix-based conjunctival flap was made. After cauterization, a midlimbal scleral groove was created. The anterior chamber was entered by a stab incision, and a can opener capsulotomy was done with an irrigating cystotome. The nucleus was removed using a lens spoon and a lens loop. The remainder of the cortex was then aspirated with a Simcoe cannula. A posterior chamber IOL (Aurolab three-piece short C model) for emmetropic correction, as calculated from A-scan value and keratometry, was used. The lens was placed in the eye under air and dialed into position. Viscoelastics were not generally used. In the case of a small posterior capsule rupture with no vitreous disturbance, the IOL was placed under a viscoelastic. The surgical wound was closed by at least five interrupted 10-O monofilament nylon sutures. When the rent was large, with or without vitreous disturbance, vitrectomy was done (manual, open sky), but the IOL was not implanted. After replacing the conjunctival flap to its original position, 0.5 ml of subconjunctival gentamicin was injected. A surgical report was completed on all patients, which included any intraoperative complications. Patients for whom it was impossible to achieve the IOL implantation were still considered as part of the assigned ECCE/PC-IOL group under an intentto-treat principle, with the implantation failure listed as an intraoperative complication. Both groups of patients were kept in the hospital for 5 postoperative days, unless complications warranted an additional period of hospitalization. On the first, third, and fifth postoperative days (and all subsequent follow-up visits), examinations using a slit lamp were done by one of two study ophthalmologists who were not part of the surgical team. During the postoperative stay, topical corticosteroids and cycloplegics were applied by a standard regimen. Follow-up visits at 2, 6, and 12 months after discharge were planned. Aphakic patients were given standard + lo-diopter glasses at the 2-month visit and prescription glasses for distance at 6 months. Upon request, pseudophakic patients were given reading glasses at the 6-month visit. The assessment of best-corrected visual acuity at 1 year represented the LENS STUDY

II: OUTCOMES

15

principal outcome of interest to establish efficacy of the interventions. Safety was assessed in terms of complications. All clinical evaluations were performed in the hospital. To facilitate comparisons between the two treatment groups, the recommendations of the Oxford Cataract Treatment and Evaluation Team (OCTET) were followed in the grading and severity scoring of each complication4: grade I, comprised of trivial complications (scores 1 through 4) that may have needed medical therapy but were not likely to result in a marked drop in visual acuity; grade II, comprised of intermediate complications (scores 5 through 8) that needed medical therapy and most likely would have resulted in a marked drop in visual acuity if left untreated; and grade III, comprised of serious complications (scores 9 through 13) that needed immediate medical or surgical intervention to prevent gross visual loss. Treatments were compared using chi-square tests for categoric variables and two-sample t tests for continuous variables. Statistical significance was established using alpha = .05 in two-sided tests.

RESULTS TABLE

1 PRESENTS

THE

BEST-CORRECTED

BASELINE

PRE-

operative visual acuity for the treated eye. More than 75% of the patients had a preoperative visual acuity of 20/600 or less. The treatment groups were comparable at baseline. Table 2 identifies the intraoperative complications common to the two randomized groups as well as complications specific to ICCE surgery and ECCE/ IOL surgery. Reported are complication events; a single patient may have experienced more than one complication. Table 3 reports the number of patients who experienced OCTET-defined severe, intermediate, or trivial intraoperative complications. Patients with multiple complications were categorized according to the complication with the highest OCTET grade. In the ICCE group, 1,602 patients (94.2%) had no intraoperative complications, and in the ECCE group, 1,644 (96.7%) had no complications (except possibly for those complications with a score of 0 reported with an asterisk in Table 2 as being of no clinical importance). 16

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TABLE 1. Preoperative Visual Acuity With Best Correction of the Treated Eye ICCE/AG Visual

Acuity

FCF/HM/PL 20/2,400-20/600 20/400-x1/240 20/200-20/120 Total

ECCE/PC-IOL

NO.

w

NO.

1,028 307 140 225

(60.5) (16.1) (8.2) (13.2)

1,022 287 14% 242

1,700 (100.0)

(“4

(60.1) (18.9) (8.8) (14.2)

1,700 (100.0)

= extracapsular cataract extraction with EWE/PC-IOL posterior chamber intraocular lens; FCF = Anger counting close to face; HM = hand movements; ICCE-AG = intracapsular cataract extraction with aphakic glasses; PL = perception of light.

The Figure presents intraoperative complication rates by surgeon for each of the three complication grades. Note the variation among surgeons, with surgeon A experiencing the lowest surgical complication rate. For serious complications, a chi-square test of uniform distribution of casesshowed an appreciable difference in the number of cases of ICCE-AG complications (I’ < .OOl) and of ECCE/PC-IOL complications (P = .016) among the four surgeons. Even though the surgeons in this study had a uniform training background, they demonstrated variable levels of surgical skill and competence. While performing ICCE, the incidence of rupture of lens capsule for surgeonsA, B, C, and D was 1.2%, 5.9%, 5.2%, and 4.0%, respectively. The incidences of vitreous loss after ICCE for surgeons A through D were 0.5%, 4.2%, 1.2%, and 0.9%, respectively. The surgeon with the maximum number of complications was also the slowest. The surgeon with the least intraoperative complications was the fastest. With regard to ECCE with PC-IOL implantation, surgeon A did not have any case of posterior capsular tears or vitreous loss. The rates of posterior capsular tears for surgeons B, C, and D were 2.4%, 3.5%, and 2.6%, whereas the rates of vitreous loss after ECCE were 1.4%, 2.6%, and 1.9%, respectively. Failure to implant a posterior chamber lens was observed in none of the cases of surgeon A, in 1.2% of the cases of surgeon B, in 4.0% of the casesof surgeon C and in 2.6% of the casesof surgeon D. Although there was no statistically significant difference between surgeons B, C, and D with regard to posterior capsular rents OF OPHTHALMOLOGY

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TABLE

2. lntraoperative

Complications

by OCTET

Grade

and Score ICCE-AG

lntraooerative

Descemet membrane tear >f/3 Bleeding in anterior chamber Shallowing of anterior chamber iris prolapse Remnants of cortex Failure to implant lridodialysis

Complications

Grade*

ECCE/PC-IOL

SCOW

NO.

I%)

NO.

I%)

t t t t t

13 84 1 2 0 9

(0.8) (3.8;

10.5) (7.0)

(0.1) (0.1) (0) (O.iq

8 119 1 8 33 4

0 1 69 29 0 0

(0) (0.1) (4.1) (1.7) (0)

7 0 0 0 21

ii

15 4 7 1

(0.4) (0) (0) to1 (1.2) io.ei

of cornea caused

by positive

vitreous

t t t t t

pressure

Sphincter tear Nucleus dislocation into vitreous Rupture of lens capsule Vitreous loss Posterior capsule ruuture with vitreous loss Posterior capsule rupture without vitreous loss Zonular dialysis/rupture with vitreous loss Zonular dialysis/rupture without vitreous loss Large remnants of viscoelastic material

I

4

I

2 10 6 10 10 6 10 5 5

Ill II Ill Ill II III II II

,o 0 ‘0

(0) (0) (0)

(0.1) (0.5) (1.9) io.2;

(0.4 (0.4) (0.1)

OCTET = Oxford Cataract Treatment and Evaluation Team. *Grade I = trivial complications (scores 1-4) requiring medical therapy but unlikely to result in a marked drop in visual acuity; grade II = intermediate complications (scores 5-8) requiring medical therapy and would likely have resulted in a marked drop in visual acuity if left untreated; grade HI = serious complications (scores 9-13) requiring immediate medical or surgical intervention to prevent gross visual loss. +lntraoperative complications that are managed successfully during surgery with no subsequent vision implications (score = 0).

TABLE

3. Distribution of Patients According to Highest OCTET Grade of lntraoperative Compli cation Experienced ICCE-AG

Complication Grade

Ill II I None Total

NO.

w

29 61 8 1,602 1,700

(1.7) (3.7) iO.5j (94.2) (100.0)

ECCEJPC-IOL Mean

Score

10.0 6.0 4.0 0.0 0.4

No.

f%)

25 22 9 1,644 1,700

(1.5) (1.3) iO.Si (96.7) (?OO.O)

Mean

Score

10.0 5.7 2.7 0.0 0.2

and vitreous loss, surgeon C chose not to implant a posterior chamber lens in 4.0% of cases. Table 4 presents the average time taken for performing each type of surgery for each of the four surgeons. Surgical time began with the conjunctival incision and ended with the subconjunctival injection. Times are shown for those cases with no complications and for those cases with serious complications. Trivial and intermediate complications were excluded from this analysis. Results from twosample t tests showed that, for both surgical proceVOL.

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dures, mean time for surgery was higher for those cases with complications compared with those cases without serious complications (P < .OOl). The surgical time was approximately double for ECCE-IOL than for ICCE. In the immediate postoperative period, the number of patients in both groups with trivial, intermediate, and serious complications was less on the fifth postoperative day compared with the first postoperative day (Table 5). In the ICCE group, serious complications were noted in 66 patients (3.9%) on day 1, in 34 patients (2%) on day 3, and in nine patients (05%) on day 5. In the ECCE-IOL group, serious complications were noted in nine patients (0.5%) on day 1, in 29 patients (1.7%) on day 3, and in seven patients (0.4%) on day 5; on day 3, the increase in serious complications was totally because of hypopyon. The specific complications reported during the first postoperative week are shown in Table 6. In general, complication rates were low by the fifth postoperative day. There were no clinically relevant differences between the two groups in the occurrence of endophLENS STUDY

II: OUTCOMES

17

ICCEIAG

a Surgeon

A

surgeon

8

Surgeon

c

surgeon

D

c

Surgeon

D

ECCE/PC-IOL

Surgeon

A 0

surgeon Trivial

m

s

Surgeon

Intermediate

FIGURE. Comparative intraoperative for the four study surgeons.

M

Serious

complication

rates

thalmitis (defined ashaving postoperative pain, eyelid swelling, chemosis of the bulbar conjunctiva, and intraocular signs of inflammation), or of hypopyon (presence of yellowish fluid in inferior portion of anterior chamber) after day 1. Shallow anterior chamber because of wound leak and pupillary block glaucoma was more common in the ICCE-AG group. Severe iritis was more common on day 5 in ECCE/ PC-IOL group. A single case of retinal detachment in the ECCE/PC-IOL group probably preexisted the surgery because it was noted 1 day postsurgery. Of the 1,700 patients who underwent ICCE, 1,672 (98.3%) completed the 2-month follow-up, 1,558 (9 1.6%) completed the 6-month follow-up, and 1,401 (82.4%) completed the final follow-up at 1 year. Of

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the 1,700 patients who underwent ECCE-IOL, 1,676 (98.6%) completed the 2-month follow-up, 1,559 (91.7%) completed the 6-month follow-up, and 1,474 (86.7%) completed the final follow-up at 1 year. All 1,700 in each group completed the day 1, 3, and 5 postoperative follow-ups. For the 2-month follow-up, the grade, score, and number of patients in each group having trivial, intermediate, and seriouscomplications are presented in Table 7. The difference in the distribution of the two treatment groups acrossthe four ordered complication grades favors ECCE-IOL and is statistically significant (P < .OOl), as it was for the intraoperative and day 1, 3, and 5 distributions, shown in Tables 3 and 5, respectively. Events of serious complications (grade III) at month 2 were in general infrequent, with no clinically relevant differences between the groups in terms of any single complication type (Table 8). Cystoid macular edema (defined by otherwise unexplained loss of vision and presence of clinically significant macular thickening) was more common in the ICCE-AG group but not at a statistically significant level (I’ = .089). Vitreous touching cornea was a common intermediate complication in the ICCE-AG group. There were only two cases(0.1%) of posterior capsular opacification impairing central vision (a grade III, serious complication) in the ECCE/PC-IOL group. At the 6-month follow-up, the distribution of trivial, intermediate, and serious complications remained similar to that at month 2, with a continued statistically significant (I’ < .OOl) difference between the two distributions (Table 7). There were no clinically relevant differences in the frequency at month 6 of serious complications such as bullous keratopathy, cornea1 edema, and endophthalmitis (Table 8). Although cystoid macular edema was significantly (P < .OOl) more common in the ICCEAG group, the difference in retinal detachment was not significant (I’ = .37). Among intermediate complications, vitreous in the anterior chamber touching the cornea and vitreous in the cornea1 section were common in the ICCE-AG group. High astigmatism, as determined by manifest correction, wasmuch more common in the ECCE/PC-IOL group (I’ < .OOl). Posterior capsular opacification with mild obscuration of the fundus was found in 109 patients (7%) and posterior capsular opacification with blurring of the OF OPHTHALMOLOGY

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TABLE

4. Average

Surgery

Time

in Minutes

by Surgeon

ICCE-AG

ECCE/PC-IOL With Serious Complications

No Complications Surgeon

A

B c D All

NO.

Mean

416

6.4 (1.8)

383 396 407 1,602

TABLE

9.8 9.8 6.7 8.1

NO.

(3.7) (2.2) (1.6) (2.9)

5. Distribution

2

5.5 (0.7)

426

12.5 (2.3) 11.4 (1.9) 8.0 (1.2) f1.2(3.0)

401 405 413 1,644

Complication Grade

No. (%)

ill 1 None

66 396 1,235 3

Total

1,700(100.0)

Ii

(3.9) (23.2) (72.6) (0.2)

12.2 6.2 2.2 0.0 3.5

No. (%)

9 (0.5) 246t14.5) 1,440 (84.7) 5 (0.3) 1,700(100.0)

ICCE-AG Mean score

12.0 5.9 2.2 0.0 2.8

No. (a)

34 200 1,412 54

(2.0) (11.8) (83.0) (3.2)

1,700

(100.0) -

fundus in three patients (0.2%) who underwent ECCE/PC-IOL. The distribution of patients across complication grades at the l-year follow-up for the two treatment groups was similar to that at months 2 and 6 (Table 7). The difference in distributions remained statistically significant (I’ < .OOl ) in favor of ECCEIPCIOL. There was no difference between treatments in the frequency at month 12 of endophthalmitis, cornea1 edema, and bullous keratopathy (Table 8). Vitreous touching the cornea, vitreous in the cornea1 section, and cystoid macular edema were more common with ICCE-AG at highly statistically significant levels (I’ < .OOl). (Th e increase in vitreous in the anterior chamber touching the cornea at the site of the section during the l-year follow-up may be caused by a predilection of the vitreous in the anterior chamber to appear as if it were in contact with the wound incision.) The relative risk (with 95% confidence intervals [CI]) for ICCE-AG compared with ECCE/ PC-IOL for these three complications was 57.3 (95% CI, 21.4 to 153.8), 14.5 (95% CI, 7.1 to 29.5), and VOL.

125,

No.

1

NO.

12.3 (2.5)

0

18.5 17.9 15.1 15.9

(3.7) (3.3) (3.5) (4.1)

MADURAI

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Mean (SD)

-

6 I? 8 25

20.3 19.4 21.0 20.1

(3.7) (3.8) (6.4) (4.6)

of Complication

Day 5

Day 3 ECCE/PC-IOL

Mean score

Mean (SD)

Accarding to the Highest OCTET Grade During t&s First Postoperative Week

Day 1 ICCE-AG

NO.

Mean (SD)

18 5 4 29

of Patients Experienced s

With Serious Complications

NO Complications

ICCE-AG

ECCE/PC-IOL Mean score

NO (?‘o)

M&Wl Score

12.2 6.7 2.0 0.0

29(1.7) 138 (8.1) 1,487(87.5) 46 (2.7)

12.0 5.9 2.0 0.0

2.7

1,700(100.0)

2.4

No. (%I

9 151 1,334 206

(0.5) (8.9) (78.5) (12.1)

1,700(100.0)

ECCE/PC-IOL Mean Score

No. (?‘a)

Mean score

12.4 7.4 1.8 0.0

7 (0.4) 99 (5.8) 1,435(84.4) 159 (9.4)

12.1 5.9 1.7 0.0

2.1

1,700(100.0)

1.8

2.7 (95% CI, 1.7 to 4.3), respectively. Retinal detachment was still more common in the ICCE-AG group but not at a statistically significant level. The high astigmatism seen at month 6 decreased markedly, related to suture removal, in the ECCE/PC-IOL group. At the l-year follow-up, posterior capsular opaciftcation with mild obscuration of the fundus was found in 127 patients (8.6%), and posterior capsular opacification with blurring was found in seven patients (0.5%) of those who underwent ECCE/PCIOL. Table 9 presents the distribution of the 3,400 randomly assigned patients across the four complication grades based on the highest grade of complication experienced by each patient throughout the 12-month follow-up period, that is, cumulative complication rates. The difference between the two distributions is highly statistically significant (P c .OOl) in favor of ECCE/PC-IOL; the difference between treatonly in serious complication ments, consisting (14.5% vs 7.7%), is also statistically significant (P < ,001). With respect to visual outcome, the efficacy endLENS STUDY

II: OUTCOMES

19

TABLE 6. Postoperative

Complications

by OCTET

Grade

and

Score

During

the

First

Postoperative

ICCE-AG

ECCE/PC-IOL No. (%)

Na (%) Postoperative

Compkation

Pain Eyelid swelling Chemosis External/subconjunctival bleeding Descemet membrane folds I0 folds Descemet membrane tear 2113 of cornea Transient cornea1 edema 3 mm blood lritis Mild: <50 cells with 2 x l-mm slit beam Severe: >50 cells Hwtwn Decentered pupil including sector iridectomy Residual cortex Visible cortical material Material covering entire pupillary area Vitreous in anterior chamber Not touching cornea Touching cornea Vitreous in anterior chamber touching cornea at site of section Pupillary block glaucoma Choroidal effusion Endophthalmitis Pupillary capture
20

Grade

Score

* * * *

Day 1

298 61 61 3

Day 3

0 (0)

16 (0.9) 43 (2.5) 1 (0.1)

2 (0.1) 15 (0.9) 2 (0.1)

(12.4) (2.2) (1.3) (0.1)

(0.4) (0.3) (0.6) (0.1)

0 (0) 4 (0.2) 1 (0.1)

1 (0.1)

1 (0.1)

1 (0.1)

I

1

149 (8.8)

93 (5.5)

65 (3.8)

I I

2 3

536 (3i .5) 172 (10.1)

230 (13.5) 52 (3.1)

67 (3.9) 6 (0.4)

II

5

38 (2.3)

26 (1.7)

12 (0.7)

2 (0.1)

4 (0.2)

0 (0)

I

4

10 (0.6)

16 (0.9)

9 (0.5)

1 (0.1)

1 (0.1)

0 (0)

I II

3 6

138 (8.1) 8 (0.5)

69 (4.1) 11 (0.6)

36 (2.1) 6 (0.4)

32 (1.9) 3 (0.2)

58 (3.4) 12 (0.7)

I II Ill

2 6 12

1,235 (72.6) 372 (21 .Q) 56 (3.3)

I

4

62 (3.6)

62 (3.6)

61 (3.6)

21 (1.2)

19 (1.1)

22 (7.3)

I

2

42 (2.4)

44

(2.6)

42 (2.5)

108 (6.3)

100 (5.9)

76 (5.1)

I

4

1 (0.1)

1 (0.1)

0 (0)

1 (0.1)

0 (0)

0 (0)

724 (42.6) 102 (6.0)

11 (0.6) 1 (0.1)

18 (1.1) 2 (0.1)

17 (1.0) 2 (0.1)

*

II

8

II Ill II III

8 13 6 13

460 (27.1) 48 (2.8)

664 (39.1) 80 (4.7)

47 (2.8)

370 (21.8) 171 (10.1)

150 (0.8) 37 (2.2)

49 (2.9) 13 (0.8)

1,405 (82.6) 229 (13.5) 9 (0.5)

1,294 (76.1) 122 (7.2) 28 (1.6)

31 (1.8) 10 (0.6)

893 (52.5) 62 (3.6) 6 (0.4)

0 (0)

0 (0) 0 (0) 0 (0)

0 (0) 0 (0) 0 (0)

2 (0.1) 0 (0) 0 (0)

2 (0.1) f (0.1) 1 (0.1)

2 (0.1) 1 (0.7) 2 (0.1)

0 (0) 0 (0)

0 (0)

49 (2.9) 24 (1.4)

52 (3.1) 25 (1.5)

52 (3.1) 26 (1.5)

0 (0)

0 (0)

I I II

0 (0) 0 (0) 0 (0)

*

0 (0) 0 (0)

OF

90 (5.3)

1 (0.1)

I

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222 (13.1)

1 (0.1)

0 P-3 0 (0)

AMERICAN

1 (0.1)

0 (0)

0 (0) 0 (0)

any vision

1 (0.1)

0 0 0 1

5 (0.3) 7 (0.4)

chamber; IOL = intraocular lens. complications not considered as having

1,309 (77.0) 62 (3.6)

0 (0) 0 (0) 0 (0) 0 (0)

1 (0.1) 10 (0.6)

II

1 (0.1)

1,352 (79.5) 129 (7.6)

1 (0.1)

6

869 (51 .l) 27 (1.6) 7 (0.4)

1,995 (70.3) 243 (14.3)

7 5 10 2

Day 5

II

1,235 (72.6) 105 (6.2) 27 (1.6)

1,212 (71.2) 75 (4.4)

210 37 22 2

Day 3

3

*

1,307 (76.9) 103 (6.1)

Oay 1

I I

1

1,227 (72.2) 146 (8.6)

Day 5

15 (0.9)

(17.5) (3.6) (3.6) (0.2)

Week

implications

12 1 1 3

(0.7) (0.1) (0.1) (0.2)

0 (0)

(score

OPHTHALMOLOGY

(0) (0) (0) (0.1)

2 (0.1) 0 (0) 0 (0) 1 (0.1)

= 0).

JANUARY

i 998

ICCE-AG

Complicatron Grade

Ill II I None Total

EWE/PC-IOL

No. (x)

Me&Xl

54 (3.2) 301 (18.0) 186 (11.2)

11.0 8.0 2.2 0.0 2.0

1,129 (67.5) l,t3?2(1QO.g)

No. (%)

ICCE-AG Mean

41 @*4) 197 (11.8) 214(1!&8) 1.224 03.0) 1,67B(lOO.O)

TABLE 8. Postoperative

No. (%)

11.2:‘.,‘:8d(5.3) 5.6 278 (17.8) I.7 77 (4.9) 0.0 1,121 {72.0) 1.2 1,55e(100.0)

Comptics.tionS

ICCE-AG

ECCE/PC-IOL Mean

NO. (%)

Il.1 7.9 3.3 0.0 2.2

by OCTET

Mean

,4T (2B) 175 (11.2) 93 (6.0) 1.250 (6il2) 1,559[100.0)

Grader,,I and

11.3 5.5 2.9 0.0 1.t

NO. I%)

‘73 293 47 988

i8.3) (20.9) (3.4) (770 5)

1,401 (lm.D]

Score at Mon,tis

Descemet membfene 510 folds

Grade

score

Month

2

Month

11.2 7.9 p.9 0.0

&i$) 145 (9 a) 68 (4-S) 1,221 182 6)

2.4

11.8 5.4 -0s 0.0

1,474(10D.O)

1.0

ECCE/PC-KJC

No 1%) Cbmplication

Mean

NO. L”h)

2, 6, and 12

ICCE.AG

Postoperatrve

ECCE/PC-IOL Mean

6

No. 1%) Month

12

MDnlh

2

Month

6

Month

12

folds

>lO folds Descemel membrane tear Xf3 of cnfnea Shallow anlerlor chamber Iris touches cornea, but space between vitreous or IOL and GOrn6a Contact between vitreous

I

1

122 (7.3)

15 (0.9)

3 (0.2)

118 (7.0)

I

s

2 (0.1)

1 [all

1 (0.1)

3 (0.2)

13 (0.8) 0 (0)

0 (0)

2 (0.1)

8

6

2 {O.l)

l(O.1)

0m

1 to 11

2 (o.lt

2 (a.1)

II

5

1 (0.1)

1 (0.1)

3 (0.2)

1 (0.1)

1 (0.1)

1 (0.1)

I.

4

76 (4.5)

87 (5.6)

76 (5.8)

26 (1.6)

27 (1.7)

20 (1.4)

and cornea

Evidence of leaking wound/ conjunctlvsl bleb Hyphema ~3 mm blodd in AC >3 mm blood lritis <50 cells with 2 X l-mm slit bear3 >50 cells Wpotwn Iris incarceration in wound Iris prolapse Decentered Pupil including sector irldactomy Residual cortex Visible corlical material Material covering entire pupillary area Vitreous in anterior chamber Not touching cornea Touching c&flea Wreous

in

touching

antefbt cornea

&&&WY

at site of sectron

Choroidal effusion Suture infection Endophthalmitis

VOL.

Continued

an next page

125,

1

NO

MADURAI

INTRAOCULAR

LENS STUDY

II: OUTCOMES

21

TABLE 8. Postoperative

Postoperative

Complication

IOP >26 mm Hg without pupillary block Filamentary keratitis Keratitis medicamentosa Cornea1 edema not resolving in 10 days Bullous keratopathy Cystoid macular edema Retinal detachment High astigmatism (13 diopters) Pupillary capture I /2 optic Malposition of haptic One loop Two loops Deposits on implant Decentered implant Traumatic extrusion of IOL Posterior capsule opacification Clear view of fundus Mild obscuration of fundus Blurring of fundus *Postoperative

complications

Complications

Grade

score

Month

8

II I II

2 6

Ill III Ill

by OCTET Grade and Score at fvlonths

2

14 (0.8) 50 (3.0) 1 (0.1)

No. (%)

Month

6

2 (0.1) 4 (0.3) 0 (0) (0.3) (0.1) (4.5) (0.3) (0.3)

12

0 (0) 0 (0)

0 (0)

I I I II Ill

2 3 4 8 13

0 0 0 0 0

0 0 0 0 0

0 (0)

*

*

II Ill

5 13

0 (0) 2 (0.1)

0 (0) 2 (0.1)

0 (0)

0 (0)

as having

any vision implications

JOURNAL

5 4 59 5 15

2

8 (0.5) 26 (1.6) 2 (0.1)

1 (0.1) 0 (0)

0 (0) 0 (0)

(0) (0) (0) (0) (0)

Month

0 (0)

1 2

AMERICAN

5 2 70 4 5

Month

I I

point, at the second-month follow-up, 326 patients (19.5%) in the ICCE-AG group had a visual acuity of 20/40 or better corrected with standard + lo-diopter glasses. In the ECCE/PC-IOL group, 514 patients (30.7%) had a visual acuity of 20/40 or better (Table 10). However, with a full manifest refraction, 1,556 patients (93.1%) of the ICCE-AG group and 1,609 patients (96.0%) of the ECCE/PC-IOL group achieved a visual acuity of 20/40 or better (data not shown). At the 6-month follow-up, 1,418 patients (91.0%) in the ICCE-AG group and 1,493 patients (95.8%) of the ECCE/PC-IOL group had a best-corrected visual acuity of 20/40 or better, with 10 (0.6%) and eight (0.5%) below 20/60 (data not shown). Because aphakic patients were given prescription glassesat 6 months, the best-corrected visual acuity was their actual visual acuity after the 6-month examination. This was not the situation with the pseudophakic 22

ECCE/PC-IOL

Ill II

not considered

(Continued)

No. (%)

7 (0.4) 1 (0.1) 42 (2.5) 1 (0.1)

(0) (0) (0) (0) (0)

12

ICCE-AG

IO IO 11 13 5

0 (0)

2, 6, and

(0.4) (0.3) (4.2) (0.4) (1.1)

6 (0.4)

6

2 (0.1) 0 (0) 0 (0) (0.5) (0.3) (1.7) (0.1) (3.7)

Month

12

0 (0) 0 (0) 0 (0)

28 (1.7) 1 (0.1) 0 (0)

8 4 26 1 58

52 (3.1) 7 (0.4)

45 (2.9) 6 (0.4)

36 (2.4) 15 (0.3)

1 (0.1)

0 (0)

Month

5 4 23 3 9

(0.3) (0.3) (1.6) (0.2) (0.6)

3 (0.2)

2 (0.1)

1 (0.1)

0 (0) 0 (0) 0 (0)

0 (0) 40 (2.4) 25 (1.5)

0 (0) 64 (4.1)

0 (0) 45 (3.1)

17 (1.1)

11 (0.7)

0 (0)

0 (0)

1 (0.1)

0 (0)

0 (0) 2 (0.1) 1 (0.1) (score

1,109 (66.2)

1,221 (78.3)

1,207 (81.9)

162 (9.7)

109 (7.0)

127 (8.6)

2 (0.1)

3 (0.2)

7 (0.5)

= 0).

patients, however, because they were not given prescription eyeglasses.(Based on visual acuity at initial examination, only 53.0% of the pseudophakic patients had a visual acuity of 20/40 or better.) At the l-year follow-up, 1,27 1 patients (90.7%) in the ICCE-AG group and 1,420 patients (96.3%) in the ECCE/PC-IOL group had a best-corrected visual acuity of 20/40 or better (Table 11). Although this difference is highly statistically significant (P < .OOl) because of the large number of patients, its clinical relevance depends on whether patients actually are refracted and prescribed corrective lenses; neither group coming to the l-year examination exhibited this level of visual acuity. Nine hundred forty-five patients (64.1%) in the ECCE/PC-IOL group had an uncorrected visual acuity of 20/40 or better at 1 year. Eighty-nine percent of ICCE-AG patients examined with their personal eyeglassesprescribed at 6 months had a visual acuity of 20/40 or better at 1 year. OF OPHTHALMOLOGY

JANu,~RY

i 998

TABLE B, DW#wtiarz of Patients According to tlse HigheaP OCTET Grade Experiencwi Throughout the 12-Month Study Per*ti

TABLE 1Q. Visual Acuity at Month 2 ICCE-AG*

Visual Acuity Complication Grade

ICCE-AG

ECCE/PC-IOL

No. l%l

No. t%)

247 685 767 1

Ill II

I None* To&l

1,700

(t4.ti) (40.3) ;as.1i (0.1)

t31

2Of20-20/4o 20/50-20160 20/60-m/200 20/240-201400 s20/600 Total

(7.7)

551 (32.41

1 ,a1 5 i59.7; 3 (0.2)

WAS UNDERTAKEN

TO PROVIDE

THE

necessary scientific evidence to fully inform policy makers, program managers, and clinicians in developing countries of the comparative safety and efficacy of ECCE/PC-IOL and ICCE-AG and of the impact of cataract surgery on patient-reported visual functioning and related quality of life. The results demonstrated the gains in visual acuity that can be achieved by cataract surgery, with a minimum of complications by either procedure. Accordingly, the procedure of choice for the cataract patient with bilateral blindness should be influenced primarily by the availability of the requisite equipment and surgical skills and secondarily by the results presented here. As evidenced in this study, marked differences in complications can exist even among adequately trained surgeons. Despite the widespread use of PC-IOL implantation, especially in developed countries,4 no randomized controlled clinical trial other than the OCTET study4 has been conducted to assessthe comparative benefit, if any, of ECCE/PC-IOL vs other cataract VOL.

125,

No. 1

($9.6) (18.8) (80.5) (0.8)

514j3D.7) 461 (27.5) 683.(40.8) 11 (0.7)

(0.5)

7P.4) 1,876 (100.0)

(100.0)

surgical procedures. Several case series reports have assessed the safety and efficacy of IOL implantation in developing-country settings.5p6 There were relatively few intraoperative complications in our study compared with an 11% incidence of vitreous loss during ECCE surgery in Malawi,7 10% incidence of ruptured posterior capsules during ECCE in Ghana,’ 10.6% incidence of posterior capsule rupture in Sierra Leone,’ and 6.4% incidence of vitreous loss in Saudi Arabia.” Primary capsulotomy was required in two thirds of the patients in the Ghana study because of a thickened primary capsule opacity. Lewallen and LeMeasurier7 attribute the higher intraoperative complication rates in developing countries to the predominant occurrence of hypermature cataracts with wrinkled tough anterior capsules and weaker zonules. Our ECCE results were similar to those reported for a series of cases at the Nepal Eye Hospital” and at the Aravind Eye Hospital.12 Factors contributing to the lower complication rate included the fact that the surgeries reported here were performed in the setting of a high-volume, high-quality facility by trained surgeons who had considerable experience in operating on advanced mature cataracts. Prospective assessment of surgeons skills is a valuable aspect of developing a high-volume, high-quality cataract program. A comparison of intraoperative complications between the ICCE and ECCE/PC-IOL patients indicates that there was no clinically relevant difference in complication frequency for those aspects of the surgery that are common to the two procedures. Among complications of serious grade in the immediate postoperative period, hypopyon and pupillary

DISCUSSION TRIAL

No. (“‘o)

With standard +1 0-diopter eyeglasses. Wmim3cted,

not

Furthermore, although only 33% of the ICCE-AG patients would have attained a visual acuity of 20/40 or better with a + lo-diopter lens, when corrected with a spherical equivalent, 1,224 patients (87.4%) achieved a visual acuity of 20/40 or better. This is nearly equivalent to the best-corrected visual acuity. (The visual acuity results do not include any of the field measurements taken on patients who could not come to the hospital for the follow-up examinations.)

PRESENT

&6 314 1,011 13 8 1,672

ECCE/PC-IOL’

1,700 (100.0)

(100.0)

*None except for the possibility of oomplications conskkwed as having any vision implications,

THE

No. (%)

MADURAI

INTRAOCULAR

LENS

STUDY

II: OUTCOMES

23

TAEtE

11. Visual

Acuity

at Month

12

ICCE-AG Correction With Personal Eyeglasses* Visual

Acuity

No. (%)

462

(33.0)

20/50-20/60

66 (6.9)

473

(33.8)

20/80-201200

41 (3.3)

432

(30.8)

20/240-20/400 c-20/600

4 (0.3) 11 (0.9)

Total

*Not

1,246

included

(100.0)

are 155 patients

Correction With Spherical Equivalent

+lO-diopter Aphakic Eyeglasses

No. (%)

1,104 (88.6)

20/20-20140

With

1,224 (87.4)

block glaucoma were more common with ICCE-AG patients. Cystoid macular edema, the serious grade complication with the highest event frequency, was more prevalent in the ICCE-AG group: at 2 months, 2.5% of the ICCE group and 1.7% of the ECCE/PC-IOL group had cystoid macular edema. This group difference was more marked (and statistically significant) at the 6-month follow-up, when 4.5% of those who had undergone ICCE showed evidence of cystoid macular edema compared with 1.7% of those who had received ECCE/PC-IOL. At the l-year follow-up, 4.2% of the ICCE group and 1.6% of the ECCE/PC-IOL group had cystoid macular edema-a relative risk of 2.7 (95% CI, 1.7 to 4.3). This controlled clinical trial confirms previous observational studies that reported this disparity in risk of cystoid macular edema between the two surgical procedures.13 There was no statistically significant difference between the two groups in the infrequent occurrence of retinal detachment, but it appears to have occurred earlier in the ICCE-AG group. At the 2-month follow-up, there was a 0.1% incidence of retinal detachment in both groups (one case each). By the 6-month follow-up, however, four patients (0.3%) who had undergone ICCE had developed retinal detachment, whereas one patient (0.1%) with ECCE/ PC-IOL had. At the final follow-up at 1 year, five patients (0.4%) with ICCE developed retinal detachment, whereas three patients (0.2%) with ECCE/ PC-IOL did. There was no difference between the two groups in the occurrence of endophthalmitis, 24

AMERICAN

JOURNAL

1,271 (90.7)

945

(64.1)

269

(19.6)

45 (3.2)

41 (2.9)

226(15.3)

5 (0.4) 19 (1.4)

4 (0.3) 18 (1.3)

(100.0)

aphakic

1,401

(100.0)

Bestcorrected

No. (%)

67 (4.8)

1,401

with personal

No. (“lo)

(7.7)

108

(100.0)

who did not present

Best-corrected

No. (%)

15 (1.1) 19 (1.4) 1,401

ECCE/PC-IOL Without Correction

No. (“6)

1,420

19 (1.3)

1 (0.1) 13 (0.9) 1,474

(100.0)

(96.3)

26 (1.8)

0 (0) 9 (0.6) 1,474

(100.0)

eyeglasses.

bullous keratopathy, or any other serious (grade III) complication. At 1 year, some form of peripheral posterior capsular opacification was present in 82% of the patients who had undergone ECCE/PC-IOL. However, this opacification was clinically unimportant and not vision threatening. Another 8.6% had a small central posterior capsular opacification that was not vision threatening but had the potential to be. Only 0.5% of patients who had undergone ECCE/PC-IOL had a serious, thick, central posterior capsular opacification that obscured vision. This study demonstrates a smaller incidence of posterior capsular opacification at 1 year compared with other studies. This may be because of the relatively short follow-up period aswell asthe maturity of the cataract. Formation of opacities on the posterior capsule after ECCE is a consequence of proliferation of lens epithelium onto the posterior capsule.l4 More than 75% of our study patients had a preoperative visual acuity of 20/600 or less, implying that the majority of them had mature cataracts. (For further study of the incidence of posterior capsular opacification, 3-year and 5-year follow-ups are planned for a random sample of these ECCE/PC-IOL patients.) The frequency of serious-grade complication events at any single evaluation time point was reasonably low for both treatment groups, with few, if any, patients experiencing multiple serious complications. (The number of patients with serious complications shown in Tables 3,5, and 7 is not much lessthan the number of severe complication events shown in the OF OPHTHALMOLOGY

JANUARY

1998

corresponding Tables 2, 6, and 8.) Furthermore, most of the patients with evidence of a serious complication at any one of the evaluation time points were not the same patients as those with a serious complication at any of the other evaluations. Cumulatively, there was a total of 359 serious complication events in the ICCE-AG group and of 205 in the ECCE/PC-IOL group (Tables 2, 6, and 8) distributed across 247 and 131 patients, respectively (Table 9). Serious cumulative complication rates were clearly higher for ICCEAG (14.7%) than for ECCE/PC-IOL (7.7%) at a statistically significant level (I’ < .OOl) and were reversed from what was used as the basis for calculating the study sample size (7% and lo%, respectively). The higher than anticipated cumulative complication rate for ICCE can be attributed to the extensive follow-up regimen, for which cumulative (longitudinal) data covering an entire year were not available from previous studies. The difference in best-corrected visual acuity between the two groups at any of the three follow-up examinations consistently favored ECCE/PC-IOL. The clinical relevance of this result depended on the timing of refraction and availability of prescription glasses. Adequate correction was required for both groups to attain good visual results. For the ICCE-AG group, in situations in which manifest refractive correction could not be provided, spherical equivalent correction was shown to be a satisfactory and simple alternative choice. This trial demonstrated that in settings in which the necessary attention to maintaining a high quality of patient care is present in the preoperative examination, intraoperative period, and postoperative follow-up examination, both procedures can produce satisfactory results. Nevertheless, ECCE/PC-IOL was shown to be superior to ICCE-AG both in terms of safety and in restoring visual acuity, and thus should be the

procedure of choice in settings that have the requisite equipment and surgical skills.

REFERENCES

I

1. Thylefors B, Negrel AD, Pararajasegaram R, Dadzie KY. Global data on blindness: an update. Bull World Health Organ 1995;73:115-121. 2. Limburg H, Kumar K, Bachani D. Monitoring and evaluating cataract intervention in India. Br J Ophthalmol 1996;SO: 951-955. 3. Natchiar GN, Thulasiraj RD, Negrel D, et al. The Madurai intraocular lens study, I: a randomized clinical trial comparing complications and vision outcomes of intracapsular cataract extraction and extracapsular cataract extraction with posterior chamber intraocular lens. Am J Ophthalmol 1998; 125:1-13. 4. Oxford Cataract Treatment and Evaluation Team. I. Cataract surgery: interim results and complications of a randomized controlled trial. Br J Ophthalmol 1986;70:402-410. 5. Hemo I. Intraocular lens implantation in an underdeveloped country. J Cataract Refract Surg 1987;13:414-416. 6. Peer J, Wood M. Intraocular lens implantation in developing countries. J Cataract Refract Surg 1990;16:621-623. 7. Lewallen S, LeMeasurier RT. Extracapsular cataract extraction in developing countries [letter]. Arch Ophthalmol 1993;lll:lS. 8. Egbert PR, Buchanan M. Results of extracapsular cataract surgery and intraocular lens implantation in Ghana. Arch Ophthalmol 1991;109;1764-1768. 9. Cook NJ. Valuation of high volume extracapsular cataract extraction with posterior chamber lens implantation in Sierra Leone, West Africa. Br J Ophthalmol 1996;80:698-701. 10. Al Faran MF. Visual outcome and complications after cataract extraction in Saudi Arabia. Br J Ophthalmol 1990; 74:141-143. 11. Ruit S, Robin AL, Pokharel RP, Sharma A, De Failer J. Extracapsular cataract extraction in Nepal. Arch Ophthalmol 1991;109:1761-1763. 12. Natchiar G, Robin AL, Nalgirkar AR, Krishnadas R. Posterior capsule tears during extracapsular cataract surgery in India. Arch Ophthalmol 1993;111:707-708. 13. Miami Study Group. Cystoid macular edema in aphakic and pseudophakic eyes. Am J Ophthalmol 1979;88:45-58. 14. McDonnell PJ, Zarbin MA, Green WR. Posterior capsule opacitication in pseudophakic eyes.Ophthalmology 1983;90: 1548-1553.

Authors Interactive@ We encourage questions and comments regarding this article via the Internet on Authors Interactive TMat http://www.ajo.com/ Questions, comments, and author responsesare posted.

VOL.

125.

No.

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MADURAI

INTRAOCULAR

LENS STUDY

II: OUTCOMES

25