Visual acuity outcomes with and without surgery in patients with persistent fetal vasculature

Visual Acuity Outcomes with and without Surgery in Patients with Persistent Fetal Vasculature George Alexandrakis, MD, Ingrid U. Scott, MD, MPH, Harry W. Flynn, Jr., MD, Timothy G. Murray, MD, William J. Feuer, MS Purpose: To investigate visual acuity outcomes in patients with persistent fetal vasculature (PFV) left untreated or treated with vitreoretinal surgical techniques and to investigate clinical features associated with prognosis. Design: Retrospective, noncomparative case series. Participants: All patients with PFV examined at the Bascom Palmer Eye Institute from January 1, 1983 through December 31, 1998. Intervention: All patients in the study had unilateral PFV. Of 42 PFV patients identified, 30 patients underwent vitreoretinal surgery. Indications for surgery included media opacity (e.g., cataract), vitreoretinal traction, and retinal detachment. Main Outcome Measures: Final best postoperative visual acuity, prognostic ocular clinical features, and surgical complications. Results: In the surgical group of patients, median age at diagnosis was 8 weeks, and median length of follow-up was 32 months, with all patients having at least 1 year of follow-up. Two patients had clinical and echographic findings consistent with anterior PFV, 2 patients had strictly posterior PFV, and the remaining 26 patients had components of both anterior and posterior PFV. Fourteen eyes (47%) achieved a final visual acuity of 20/400 or better at last follow-up. Risk factors for a poor visual acuity outcome (⬍20/400) included microphthalmia (28% of patients with microphthalmia versus 67% of patients with normal axial length achieved a final vision of 20/400 or better; P ⫽ 0.061) and preoperative retinal detachment or retinal or optic nerve abnormalities, or both, such as hypoplasia, folds, or indistinct macula with hypopigmentation (25% of patients with any of these anomalies versus 61% of patients without these findings achieved a final vision of 20/400 or better; P ⫽ 0.072). After surgery, retinal detachment developed in three eyes, chronic hypotony in two other eyes, and neovascular glaucoma in one eye. In the nonsurgical group there were 6 male and 6 female patients. Two patients with posterior PFV had minimal disease and were not considered surgical candidates, whereas 10 patients with combined anterior and posterior PFV had advanced pathologic features, and it was believed that surgery would not offer significant visual improvement; median age at diagnosis was 9.5 months, and median length of follow-up was 36 months, with all patients having at least 1 year of follow-up. At last follow-up, 3 eyes (25%) had a final visual acuity of 20/400 or better. During follow-up, retinal detachment developed in 2 eyes and chronic hypotony in an additional 2 eyes. Conclusions: The current study indicates that approximately 50% of patients undergoing surgery for PFV will achieve useful vision. Visual acuity outcomes in patients with PFV are correlated with the nature and extent of ocular risk factors. Some patients may not be candidates for surgery because of either minimal changes or advanced disease that limit the potential of visual improvement. Ophthalmology 2000;107:1068 –1072 © 2000 by the American Academy of Ophthalmology. Persistent hyperplastic primary vitreous is a term originally coined by Reese1,2 in 1949 to describe an idiopathic, sporadic congenital syndrome. It is usually an isolated monocOriginally received: October 13, 1999. Accepted: March 1, 2000. Manuscript no. 99702. Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida. Supported in part by Fight for Sight, Inc., New York, New York. Correspondence to Harry W. Flynn, Jr., MD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136.

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© 2000 by the American Academy of Ophthalmology Published by Elsevier Science Inc.

ular finding and was initially thought to represent an abnormal regression of the primary vitreous and hyaloid vasculature. Persistent hyperplastic primary vitreous may be associated with rare systemic syndromes, such as WalkerWarburg anencephaly, oculo-dento-osseous dwarfism, or oculo-palato-cerebral dwarfism, and may be bilateral, especially in association with Norrie’s disease.3,4 Persistent hyperplastic primary vitreous presents in an otherwise healthy newborn with a spectrum of ocular anomalies including microphthalmia, progressive cataract, retrolental fibrovascular tissue, persistent hyaloid vessel remnants, and tunica ISSN 0161-6420/00/$–see front matter PII S0161-6420(00)00100-7

Alexandrakis et al 䡠 Visual Outcomes in PFV vasculosa lentis remnants. Goldberg3 suggested that the term persistent hyperplastic primary vitreous be replaced by the term persistent fetal vasculature (PFV) because the latter describes more accurately the anatomic and pathologic features of the disease. Several studies have recommended early surgical intervention for patients with PFV to preserve the globe and prevent such complications as angle-closure glaucoma, retinal detachment, and phthisis.5–15 More recent studies have reported improved outcomes in surgical intervention of PFV, probably the result of earlier diagnosis, more careful case selection for surgery, improved surgical techniques, and aggressive postoperative amblyopia therapy.5,6 The purpose of the current study was to evaluate the visual acuity outcomes of PFV patients untreated or treated with vitreoretinal surgery and to compare the surgical results with those reported in other published series.

Patients and Methods The study protocol was approved by the Institutional Review Board of the University of Miami School of Medicine. The medical records of all patients with the diagnosis of PFV evaluated at the Bascom Palmer Eye Institute from January 1, 1983 through December 31, 1998 were reviewed retrospectively. Indications for surgery included media opacity (e.g., cataract), vitreoretinal traction, and retinal detachment. Patients with either mild or advanced PFV for whom it was not believed that surgery would offer significant visual improvement were observed. The following information was recorded for each patient: age at diagnosis, sex, race, eye involved, associated systemic abnormalities, clinical features, visual acuity, intraocular pressure, axial length (based on echography), surgical procedure performed, intraoperative or postoperative complications, type of aphakic rehabilitation, amount of amblyopic patching therapy, compliance with amblyopia therapy, and length of follow-up. Ancillary tests included A-scan and B-scan ophthalmic ultrasound. Microphthalmia was defined based on previously published normal axial length measurements stratified by age.16,17 Visual acuity was assessed with age-appropriate tests such as the Teller, BVAT-Allen, and Snellen methods; in younger patients, fixation patterns were recorded. Amblyopia therapy consisted of patching the better eye for several waking hours every day with placement of a contact lens on the involved eye. The contact lens power was checked approximately every 3 months and replaced if necessary. Persistent fetal vasculature was classified as anterior if a retrolental fibrovascular membrane, elongated ciliary processes, or cataract were present on clinical examination. Persistent fetal vasculature was classified as posterior when one or more of the following clinical features was associated with an elevated vitreous membrane or stalk from the optic nerve: (1) a retinal fold or retinal dysplasia, (2) retinal detachment, or (3) optic nerve hypoplasia. Thirty-five of the 42 PFV patients in the current series had features of both anterior and posterior PFV and were classified as having combined PFV.

Results Forty-two eyes of 42 patients with PFV were identified and included in this study. Thirty eyes of 30 patients with PFV under-

went surgical repair. Patient data for the surgical and nonsurgical groups are summarized in Tables 1 and 2, respectively. No patient in the current study had a known associated systemic illness or malformation.

Surgical Group In the group of 30 patients who underwent surgical treatment, there were 17 male and 13 female patients. The right eye was involved in 18 cases and the left eye in 12 cases. The age at diagnosis of PFV ranged from 1 week to 10 years, with a median age at diagnosis of 8 weeks. Median length of follow-up was 32 months, with all patients having at least 1 year of follow-up. Two patients had clinical and echographic findings consistent with anterior PFV, 2 patients had strictly posterior PFV, and the remaining 26 patients had components of both anterior and posterior PFV. Six had a tractional retinal detachment (TRD) at presentation; four patients had retinal dysplasia, folds, or indistinct macula; and two patients had optic nerve hypoplasia or dysplasia. Mean age at the time of surgery was 16 months (range, 2 weeks–10 years). The 2 patients with strictly posterior PFV underwent a pars plana vitrectomy, and the remaining 28 patients underwent a primary pars plana lensectomy and vitrectomy procedure. Of the latter 28 patients, 12 also had a membrane peeling procedure and 2 underwent a scleral buckling procedure at the time of vitrectomy for a TRD. Two patients had a posterior chamber intraocular lens placed at the time of lensectomy. There were no intraoperative complications. At last follow-up, 14 eyes (47%) had a final visual acuity of 20/400 or better and 6 eyes (20%) achieved a final visual acuity of 20/100 or better. Ten of the 14 patients (71%) with vision acuity at final follow-up of 20/400 or better were 4 months of age or younger at presentation. The mean age of the patients at last follow-up was 5.3 years. Postoperative events included rhegmatogenous retinal detachment (RRD) in 3 eyes, chronic hypotony in 2 eyes, and neovascular glaucoma in 1 eye. The eye with neovascular glaucoma was eventually enucleated. One patient (patient 6) underwent scleral buckling procedure for a postoperative RRD, with a visual acuity of 20/40 at the last follow-up visit. Microphthalmia (based on A-scan echography measurements) and preoperative RRD or retinal or optic nerve abnormalities (such as hypoplasia, folds, or indistinct macula with hypopigmentation) were associated with a poor visual outcome (⬍20/400). Microphthalmia was defined based on previously published normal axial length measurements stratified by age.16,17 Only 5 of the 18 patients (28%) with microphthalmia versus 8 of the 12 patients with normal axial length (67%) achieved a final visual acuity of 20/400 or better (P ⫽ 0.061). Only 3 of the 12 patients (25%) with preoperative RRD or evidence of retinal or optic nerve abnormalities, versus 11 of the 18 patients (61%) without these anomalies, achieved a final vision of 20/400 or better (P ⫽ 0.072). Postoperative amblyopia therapy was administered in 25 of the 30 patients; the remaining 5 patients did not undergo amblyopia therapy because it was believed that there was no potential for useful visual acuity after surgery and the goal of surgery was to preserve the globe (patients 19 –21, 28, and 29). Amblyopia therapy consisted of an aphakic soft contact lens (placed 1– 4 weeks after surgery) in 23 patients, whereas 2 patients had a posterior chamber intraocular lens placed at the time of surgery (patients 14 and 17). Occlusion of the better eye ranged from 4 hours to full-time patching for the waking hours each day. At least 5 of the 25 patients had poor compliance with amblyopia treatment (patients 2, 18, 24, 26, and 27). There was no significant difference in presenting or final visual acuity between the 5 noncompliant patients compared with the 20 compliant patients.

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Ophthalmology Volume 107, Number 6, June 2000 Table 1. Surgical Group Patient Data Interval between Anterior/ Patient Age at Diagnosis Posterior Follow-up No. Sex Eye Diagnosis and Surgery PFV (mos) 1 2 3

F M F

LE RE LE

4 mos 1 wk 10 yrs

3 days 4 wks 4 wks

A A P

12 130 46

4 5 6

M M F

LE RE RE

2 mos 4 mos 3 mos

2 days 3 days 6 wks

P A/P A/P

69 34 93

7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

M M M M M M F F F F F F M M M M M M F

RE RE RE LE LE RE RE RE RE LE LE LE LE LE LE RE RE LE RE

5 wks 1 mo 17 mos 2 mos 6 yrs 1 mo 2 wks 1 wk 42 mos 1 mo 24 mos 34 mos 3 mos 2 mos 1 wk 2 mos 4 mos 1 wk 1 mo

2 days 1 wk 2 days 1 day 3 days 5 days 1 wk 8 wks 1 wk 4 wks 4 mos 6 wks 2 days 1 day 3 days 3 days 2 days 4 wks 7 wks

A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P A/P

43 119 30 127 36 16 45 12 100 62 30 92 108 12 12 12 15 12 24

26

F

RE

2 mos

2 wks

A/P

27

27 28

F M

RE RE

2 wks 5 mos

3 wks 9 wks

A/P A/P

12 24

29 30

M F

RE RE

2 mos 2 wks

7 wks 1 wk

A/P A/P

45 26

Initial VA BR BR LP

Final VA 20/400 5/200 20/400

Procedure

Amblyopia Treatment

Comment

L/V L/V/MP V

CL/patch Noncompliant CL/patch TRD, retinal dysplasia BR 20/400 V CL/patch Fix/follow 20/30 L/V/MP CL/patch Fix/follow 20/40 L/V/MP CL/patch Postoperative RRD, underwent SBP Fixes 20/50 L/V CL/patch BR 20/70 L/MP CL/patch BR 20/80 L/V/MP CL/patch BR 20/100 L/V CL/patch 20/400 20/200 L/V CL/patch Retinal dysplasia BR 20/200 L/V/MP CL/patch Retinal dysplasia BR 20/300 L/V Noncompliant BR 20/400 L/MP CL/patch 20/300 20/400 L/V PCIOL/patch BR 4/200 L/V CL/patch BR 4/200 L/V PCIOL/patch LP 1/200 L/V CL/patch BR HM L/V/MP None ONH Fixes LP L/V/MP None TRD BR LP L/V None TRD Fixes Fixes L/V/SBP CL/patch TRD BR Fixes L/V CL/patch TRD BR Fixes L/V Noncompliant BR Fixes L/V/MP CL/patch Retinal dysplasia, ONH BR NFF L/V Noncompliant Retinal dysplasia, hypotony BR NFF L/V Noncompliant Postoperative RRD BR NFF L/V None Preoperative RRD, hypotony BR NLP L/V/MP/SBP None Postoperative RRD BR Enucleated L/V/MP CL/patch Postoperative NVG

A ⫽ anterior PFV; BR ⫽ blink reflex; CL ⫽ contact lens; F ⫽ female; HM ⫽ hand motions; L ⫽ lensectomy; LE ⫽ left eye; LP ⫽ light perception; M ⫽ male; MP ⫽ membrane peeling; NFF ⫽ no fix and follow; NLP ⫽ no light perception; NVG ⫽ neovascular glaucoma; ONH ⫽ optic nerve hypoplasia; P ⫽ posterior PFV; PCIOL ⫽ posterior chamber intraocular lens; PFV ⫽ persistent fetal vasculature; RRD ⫽ rhegmatogenous retinal detachment; SBP ⫽ scleral buckle procedure; TRD ⫽ tractional retinal detachment; V ⫽ vitrectomy; VA ⫽ visual acuity.

Nonsurgical Group In the group of 12 patients who were observed, there were 6 male and 6 female patients. The right eye was involved in 9 patients and the left eye in 3 patients. The age at diagnosis of PFV ranged from 1 to 48 months, with a median age at diagnosis of 9.5 months. Median length of follow-up was 36 months, with all patients having at least 1 year of follow-up. Three patients had clinical and echographic findings consistent with posterior PFV, and the remaining 9 patients had components of both anterior and posterior PFV. The decision to observe was based on the presence of mild PFV (2 patients), foveal or optic nerve hypoplasia or both (6 patients), marked microphthalmia (3 patients), and inoperable RRD (1 patient). At last follow-up, 3 of the 12 eyes (25%) had a final visual acuity of 20/400 or better, and 2 eyes (17%) achieved a final visual acuity of 20/100 or better. During follow-up, a localized TRD developed in 1 eye, a combined TRD/RRD developed in 1 eye, and chronic hypotony developed in an additional 2 eyes. The retinal detachments in these two eyes were not surgically repaired because of limited potential for visual recovery. Amblyopia therapy was initiated promptly in all patients in this group,

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except the patient with inoperable RRD because it was believed that there was no potential for useful visual acuity. Occlusion of the better eye ranged from 4 hours to full-time patching for the waking hours each day.

Discussion The reported visual acuity results after surgery for PFV are variable.5– 8 It is thought that patients with strictly anterior PFV have a generally good visual potential, in contrast to patients with posterior PFV in whom visual potential is often limited by coexisting retinal and optic nerve abnormalities.3,5 Bilaterality may also be associated with outcome, because bilaterally affected children with PFV may be more likely to have a posterior component.4 A comparison of the published studies on the surgical outcomes of PFV is summarized in Table 3. In 1986, Karr and Scott7 reported 8 of 23 PFV patients (35%) with 20/400

Alexandrakis et al 䡠 Visual Outcomes in PFV Table 2. Nonsurgical Group Patient Data

Sex

Eye

Age at Diagnosis (mos)

1 2 3 4 5 6 7 8 9

M F F M M M M F F

RE RE RE LE RE RE RE RE RE

18 48 9 30 26 48 2 5 3

P P P A/P A/P A/P A/P A/P A/P

36 36 36 36 108 66 126 24 42

20/80 6/200 Fixes FF NFF 4/200 Fixes NFF NLP

20/100 20/200 Fixes 20/50 5/200 4/200 2/200 NLP NLP

10 11 12

M F F

LE LE RE

1 1 10

A/P A/P A/P

12 96 14

NFF NFF NFF

NLP NLP NLP

Patient No.

Anterior/ Posterior PFV

Follow-up (mos)

Initial VA

Final VA

Reason for Observation Mild PFV Foveal hypoplasia Foveal hypoplasia Mild PFV Foveal hypoplasia Foveal hypoplasia Foveal hypoplasia Inoperable RD, ONH Foveal and optic nerve hypoplasia Marked microphthalmia Marked microphthalmia Marked microphthalmia

Comment

Localized TRD Hypotony TRD/RRD

Hypotony

A ⫽ anterior PFV; F ⫽ female; FF ⫽ fix and follow; LE ⫽ left eye; M ⫽ male; NFF ⫽ no fix and follow; NLP ⫽ no light perception; ONH ⫽ optic nerve hypoplasia; P ⫽ posterior PFV; PFV ⫽ persistent fetal vasculature; RD ⫽ retinal detachment; RRD ⫽ rhegmatogenous retinal detachment; RE ⫽ right eye; TRD ⫽ tractional retinal detachment; VA ⫽ visual acuity.

or better vision after surgery. In 1991, Pollard8 reported that 17% of patients achieved a final visual acuity of 20/100 or better after surgery, contact lens fitting, and amblyopia therapy. In 1998, Mittra et al6 reported the visual outcomes of 14 patients with combined anterior and posterior PFV after lensectomy and vitrectomy; 10 eyes (71%) achieved a visual acuity of 20/300 or better and 8 eyes (57%) achieved a final visual acuity of 20/100 or better. In 1999, Dass and Trese5 reported the outcomes of PFV in 35 eyes of 27 patients; 19 of the eyes had components of both anterior and posterior disease. Initial lensectomy and vitrectomy was performed in 24 eyes (68.6%), and the reoperation rate was 32.3%. Six eyes (17%) achieved a final visual acuity of 20/800 or better. In the current study, 14 of the 30 eyes (47%) in the surgical group and 3 of the 12 eyes (12%) in the nonsurgical group achieved a final visual acuity of 20/400 or better at the last follow-up visit. Microphthalmia and preoperative RRD or retinal or optic nerve abnormalities such as hypoplasia, folds, or indistinct macula with hypopigmentation were associated with a poor visual outcome. Although these associations did not reach statistical significance (in our

opinion because of a small sample size), we believe they are clinically relevant. Age at PFV diagnosis may also be associated with visual outcome; 10 of the 14 patients with a final vision of 20/400 or better were 4 months of age or younger at presentation; again perhaps because of a small sample size, this was not statistically significant. The limitations of our study include its retrospective nature, lack of randomization to the two management groups, and analysis of data from a single institution. The visual prognosis in patients with PFV is often poor, especially in the posterior form of the disease. Surgical treatment may not be effective in patients with severe microphthalmia or advanced posterior PFV, such as marked foveal hypoplasia, dysplasia, or RRD. These patients (as well as patients with only mild clinical PFV findings, such as a partial vitreous stalk) may need only to be observed. However, the current study confirms that patients with combined anterior and posterior PFV may achieve useful vision after surgical treatment in conjunction with postoperative amblyopia therapy. In these very young patients, amblyopia therapy is important in visual recovery after combined lensectomy and vitrectomy for PFV and requires the joint

Table 3. Comparison of Published Studies on the Surgical Outcomes of Persistent Fetal Vasculature (PFV)

Study (yr)

No. Eyes Undergoing Surgery

No. Eyes with Combined Anterior and Posterior PFV

Final VA 20/400 or Better (Eyes with Combined PFV)

Average Follow-up (mos)

Bilateral Cases

Federman et al9 (1982) Stark et al10 (1983) Karr and Scott7 (1986) Pollard8 (1991) Cheung et al11 (1997) Mittra et al6 (1998) Dass and Trese5 (1999) Current series (2000)

7 7 23 46 20 14 29 30

NA NA 15 28 15 14 19 26

0 43% 35% 20% 30% 71% 21% 47%

15 51 59 NA 36 22 37 48

1 0 1 2 0 0 7 0

PFV ⫽ persistent fetal vasculature; VA ⫽ visual acuity.

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Ophthalmology Volume 107, Number 6, June 2000 effort of the ophthalmologist, contact lens specialist, and parents.6 However, amblyopia therapy may be of limited value in patients with severe retinal or optic nerve dysplasia or hypoplasia. In addition, some degree of amblyopia may develop in patients with PFV even with amblyopia treatment, given the large degree of anisometropia that is present in a microphthalmic, PFV eye. Studies have shown that patients with PFV may be at risk for the development of glaucoma, RRD, and vitreous hemorrhage even after surgical repair.6 – 8 Therefore, continued follow-up of these patients is important to ensure proper treatment of these complications if they occur. The patient’s age at diagnosis, amblyopia therapy, and, if indicated, the timing of vitreoretinal surgery are important in achieving the best final vision in patients with PFV. Although useful vision may be achieved in eyes with PFV, the severity of pre-existing microphthalmia and retinal or optic nerve abnormalities may limit final vision.

References 1. Reese AB. Persistence and hyperplasia of primary vitreous; retrolental fibroplasia-two entities. Arch Ophthalmol 1949;41: 527–52. 2. Reese AB. Persistent hyperplastic primary vitreous. The Jackson Memorial Lecture. Am J Ophthalmol 1955;40:317–31. 3. Goldberg MF. Persistent fetal vasculature (PFV): an integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture [review]. Am J Ophthalmol 1997; 124:587– 626. 4. Marshman WE, Jan JE, Lyons CJ. Neurologic abnormalities associated with persistent hyperplastic primary vitreous. Can J Ophthalmol 1999;34:17–22. 5. Dass AB, Trese MT. Surgical results of persistent hyperplastic primary vitreous. Ophthalmology 1999;106:280 – 4.

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6. Mittra RA, Huynh LT, Ruttum MS, et al. Visual outcomes following lensectomy and vitrectomy for combined anterior and posterior persistent hyperplastic primary vitreous. Arch Ophthalmol 1998;116:1190 – 4. 7. Karr DJ, Scott WE. Visual acuity results following treatment of persistent hyperplastic primary vitreous. Arch Ophthalmol 1986;104:662–7. 8. Pollard ZF. Results of treatment of persistent hyperplastic primary vitreous. Ophthalmic Surg 1991;22:48 –52. 9. Federman JL, Shields JA, Altman B, Koller H. The surgical and nonsurgical management of persistent hyperplastic primary vitreous. Ophthalmology 1982;89:20 – 4. 10. Stark WJ, Lindsey PS, Fagadau WR, Michels RG. Persistent hyperplastic primary vitreous. Surgical treatment. Ophthalmology 1983;90:452–7. 11. Cheung JC, Summers CG, Young TL. Myopia predicts better outcome in persistent hyperplastic primary vitreous. J Pediatr Ophthalmol Strabismus 1997;34:170 – 6. 12. Laatikainen L, Tarkkanen A. Microsurgery of persistent hyperplastic primary vitreous. Ophthalmologica 1982;185: 193– 8. 13. Reynolds JD. Visual acuity after treatment of persistent hyperplastic primary vitreous [letter]. Arch Ophthalmol 1986; 104:1274, 1277. 14. Scott WE, Drummond GT, Keech RV, Karr DJ. Management and visual acuity results of monocular congenital cataracts and persistent hyperplastic primary vitreous. Aust N Z J Ophthalmol 1989;17:143–52. 15. Haddad R, Font RL, Reeser F. Persistent hyperplastic primary vitreous. A clinicopathologic study of 62 cases and review of the literature. Surv Ophthalmol 1978;23:123–34. 16. Grignolo A, Rivara A. Biometry of the human eye from the sixth month of pregnancy to the tenth year of life. In Vany´sek J, ed. Diagnostica Ultrasonica in Ophthalmologia. Brno: Universita J E Pukyne, 1968;251–7. 17. Grignolo A, Rivara A. Biometric observations on the eyes of infants born at full term and of premature infants during their first year [in French]. Ann Ocul (Paris) 1968;201:817–26.