A novel vitreous substitute of using a foldable capsular vitreous body injected with polyvinylalcohol hydrogel

Abstract

Hydrogels may be the ideal vitreous substitutes due to their wonderful physical features and biocompatibility. However, their drawbacks, short residence time, and biodegradation in vivo, have led to the fact that none of them have been approved for clinical use. In this study, we developed a novel approach of using a foldable capsular vitreous body (FCVB) injected with polyvinylalcohol (PVA) hydrogel as a vitreous substitute for long-term tamponade. The 3% PVA hydrogel that was cross-linked by gamma irradiation showed good rheological and physical properties and had no toxicity in vitro. After 180 days retention, the 3% PVA hydrogel inside FCVB remained transparent and showed good viscoelasticity without biodegradation and showed good biocompatibility and retina support. This new approach may develop into a valuable tool to improve the stability performance of PVA hydrogel as a vitreous substitute and to extend the application function of FCVB for long-term implantation in vitreous cavity.

Figure 1

(A) The storage modulus G′ and the loss modulus G″ were plotted logarithmically against frequency (0.01–10 Hz at 37°C) for the 1% PVA, 3% PVA, and 7% PVA hydrogels. (B) The storage modulus G′ and the loss modulus G″ were plotted logarithmically against frequency (0.01–10 Hz at 37°C) for the silicon oil and HA.

Figure 2

(A) The loss tangent was plotted logarithmically against frequency (0.01–10 Hz at 37°C) for the 1% PVA, 3% PVA, and 7% PVA hydrogels and for a silicon oil, HA. (B) Creep compliance was plotted logarithmically against time for the 1% PVA, 3% PVA, and 7% PVA hydrogels.

Figure 3. The storage modulus G′ and the loss modulus G″ were plotted logarithmically against frequency (0.01–10 Hz at 37°C) for 3% PVA hydrogel before and after injection through a 19-gauge needle.

Figure 4

(A) Cytotoxicity using L929 fibroblasts cell culture in different samples extracts (1% PVA, 3% PVA, 7% PVA, 1% PVA + FCVB, 3% PVA + FCVB, and 7% PVA + FCVB). No changes in cell morphology were observed in any groups (200×). (B) MTT assay at 24, 48 and 72 hours. No significant difference among sample extracts as compared to the negative control (P > 0.05) was observed.

Figure 5. Ninety days and one hundred eighty days follow-up examinations using a slit-lamp.

(A1–A1′) The anterior segment was shown to be normal after 90 days in the BSS group. (A2–A2′) The anterior segment was shown normal after 180 days in the BSS group; (B1–B1′) No inflammation reaction or other disease emerged in the anterior segments of the eyes after 90 days in the PVA group, except for a slight complicated cataract. (B2–B2′) The complicated caratact was aggravated after 180 days in the PVA group. (C1–C1′) The eye was aphakic without any abnormalities in cornea or anterior chamber after 90 days in the PVA + FCVB group. (C2–C2′) The cornea and anterior chamber of the eye remained very clear after 180 days in the PVA + FCVB group.

Figure 6. Postoperative posterior fundus photograph of the three groups' eyes.

All eyes showed clarity in the vitreous cavities, except that the eyes of PVA group appeared to be mildly blurry after 180 days due to complicated cataracts. B-scan ultrasonography showed all eyes' had good retina attachment and a smooth curve epiretinal echo enhancement in the FCVB eye (white arrow), indicating that the FCVB has a good retina-support function.

Figure 7. Intraocular pressure changes during the 180-day follow-up.

On postoperative day 3, an increasing tendency in the BSS group and in PVA group and a decreasing tendency in the PVA + FCVB group were observed, and the differences were significant among the three groups (*P < 0.05). No significant elevation of intraocular pressure was observed after 7, 14, 30, 60, and 90 days among the three group (P > 0.05).

Figure 8

Scotopic ERG waveforms (A) and the photopic ERG waveforms (B) of the three groups after 180 days, as well as the amplitude of the ERG after operation. (C) Change in the amplitude of the scotopic ERG after 90 days and 180 days. The decrease in a-wave and b-wave amplitudes was significant in the PVA + FCVB group after 90 days and 180 days as compared to the other two groups (P < 0.05). (D) Change in the amplitude of the photopic ERG after 90 days and 180 days. The decrease in the a-wave and b-wave amplitudes was significant in the PVA + FCVB group after 90 days and 180 days as compared to the other two groups (P < 0.05).

Figure 9. Appearance of the eyeball specimens in the PVA + FCVB group and the PVA group.

(A1–A3) The FCVB-supported retina operates perfectly in the vitreous cavity after 180 days, and the FCVB injected with 3% PVA hydrogel was clear and transparent. (B1–B3) The vitreous cavity in the PVA group was still full of 3% PVA hydrogel after 90 days, and the 3% PVA hydrogel remained very clear and transparency. (C1–H2) Histology revealed the normal structure and cell morphology of the cornea, ciliary body, and retina in the three groups' eyes after 90 days and 180 days. H3: Retinal disorder was seen in the PVA + FCVB group eyes after 180 days. The retina displayed an aggregation of the inner nuclear layer and the outer nuclear layer and a thinning of the ganglion cells layer. (H&E staining: conera and ciliary body, ×100; retina, ×200).

Figure 10

(A) Comparison of the dynamic viscoelastic moduli for the 3% PVA hydrogel before and after 90 days tamponade. (B) Comparison of the dynamic viscoelastic moduli for the 3% PVA hydrogel before and after 180 days tamponade.

Figure 11. An FCVB was folded and implanted into a vitreous cavity during PPV surgery.

I: Illustration of FCVB implantation. II: Rabbit surgical procedures. (A) A standard three-port PPV was performed to remove the vitreous. (B–C) The FCVB was folded and implanted into the vitreous cavity. (D–E) The PVA hydrogel was injected into the capsule through the valve. (F) fixing the tube-valve device under the conjunctiva.