Cataract is one of the most frequent complications of uveitis, which can be induced by chronic inflammatory response and use of corticosteroids . Surgery is generally considered as the only effective therapeutic strategy for uveitis complicated with cataract, and the commonly used surgical strategies include extracapsular extraction, intracapsular extraction, lensectomy, and phacoemulsification . At present, the surgical program for uveitic cataract mainly depends on the experience of doctors. There is still no clear standard for the selection of scrupulous cases, indications and contraindications, surgical techniques, and operation time [5, 27]. Foster et al. have described four indications for cataract surgery in patients with a history of uveitis, including phacoantigenic uveitis (active inflammation as a result of leak-age of lens proteins), visually significant cataract, cataract that impairs fundus assessment in cases with suspected fundus pathology, and cataract that precludes adequate visualization of the posterior segment in cases undergoing posterior segment surgical procedure . In this study, all the enrolled patients with uveitis-induced cataract belong to the indication of visually significant cataract, and the phacoemulsification with clear-cornea incision combined with intraocular lens implantation were performed. Except the need of immediate mandatory cataract extraction for phacoantigenic uveitis, preoperatively control of inflammation for at least 3 months has become the guarantee of successful surgery. A meta-analysis based on 89 articles has shown that among uveitic eyes with quiet uveitis before cataract surgery, visual acuity of 20/40 or better was achieved in 68% following phacoemulsification, 72% following extracapsular cataract extraction, and 40% following pars plana lensectomy . On the contrary, active uveitis at the time of cataract surgery was associated with worse visual outcomes . Consistent with this consensus, all patients enrolled in this study had no systemic medication within 3 months, and 71.43% patients had no topical medication for at least 3 months before the surgery. Encouragingly, an obvious improvement in visual gain (BCVA > 0.5) was revealed in call cases. Glaucoma is another potentially blinding complication of uveitis, which can be induced by inflammation, secondary corticosteroid response, and angle abnormalities . The surgery is thought to be necessary for glaucoma patients who cannot control the inflammation by drugs. Here, obvious improvement in visual gain was also revealed in one case maintaining topical eye drops of glucocorticoid before the surgery. The surgery may be conducive to the excretion of immune complexes, prostaglandins, and toxic substances in aqueous humor, thereby controlling intraocular pressure and inflammatory reaction.
Although the cataract surgery achieves relatively good outcome on visual gain in patients with uveitic cataract, postoperative complications and recurrence are still difficult problem to solve. For example, Rahman I et al. have shown that during a minimum follow-up of 5 years, 24% macular oedema or scarring, 96% posterior capsule opacification, 15% glaucoma drainage were found in 61 patients underwent cataract extraction with intraocular lens implantation . Yangzes S et al. have revealed that the complications of visual axis opacification (39.66%), cystoid macular edema (31.03%), and glaucoma (8.62%) were common in total 58 eyes underwent cataract surgery . Here, only the occurrence of keratic precipitates was found in 2 cases after the surgery. This complication may be attributed to the prolonged inflammatory response induced by local dysimmunity. There is nothing to worry that the keratic precipitates was recovered within 1 week. On the other hand, the recurrence risk of uveitis remains. Zhang Y et al. have found that uveitis recurred in 14 eyes (18.9%) within 3 months and inflammation recurred in 34 eyes (45.9%) in the whole follow-up period . Balta O et al. have determined that the incidence of postoperative recurrence of uveitis was 52.7% in 48 patients underwent cataract surgery during 4 years of follow-up . Therefore, avoiding postoperative recurrence has become a great challenge in clinical practice. In this study, in addition to the phacoemulsification with clear-cornea incision, and intraocular lens implantation, pupil coroplasty was also performed in patients with uveitic cataract. Encouragingly, no recurrence of uveitis was found in 96.43% cases (n = 27) during the follow-up of 5-10 years. The findings on the underlying pathological mechanism of chronic uveitis showed that the lymphocytes in patients with uveitis exhibit great resistance to apoptosis, resulting in long-term existence of autoreactive lymphocytes, and subsequently leading to the chronicity and recurrence of uveitis. In addition, the destruction of blood aqueous barrier induced by inflammation leads to severe damage of iris microcirculation through enhancing the permeability of blood vessels and weakening the barrier function. Then freely released immune cells and inflammatory mediators directly contribute to the expansion of inflammatory injury. Therefore, we speculated that the low recurrence of uveitis revealed in this study may be attributed to the removal of pathological tissues to some degrees. Furthermore, the only patient with recurrent uveitis attributed to immunosuppression induced by the onset of ankylosing spondylitis. Our results indicated that pupil coroplasty may reduce the recurrent risk of uveitis due to iris inflammation. However, the inflammation induced by other immunologic disorders is still inevitable for the recurrence of uveitis.
A previous study based on equine experimental uveitis has observed the histopathological characteristics of engorgement of blood vessels, neovascularization, focal or diffuse mononuclear proliferation, exudative retinal detachment, and disorganization of retinal layers . In order to discover the underlying pathological mechanism of uveitis in human, HE staining was performed to reveal the histopathological changes of uveitis-suffered iris tissues in this study. An obvious atrophy of iris stroma was observed in all cases, which is considered as a prominent feature of uveitis. The inflammation-induced immune abnormality may contribute directly to the iris atrophy in uveitis. Notably, the iris atrophy can also be observed in uveitis at a quiescent period, which is considered as one of the potential causes of recurrence. Since iris cells have an ability to bind and accumulate drugs , the atrophy of iris tissues may also contribute to the recurrent of uveitis via inhibiting the combination and reactivity of drugs. In this study, we also observed the hyperplasia of pigment cells in the pigment epithelium and stroma in 32.14% and 67.86% cases, respectively. This phenomenon may be explained that the local immune injury greatly influences the normal structure of iris tissue, leading to the abnormal proliferation of pigment cells. Inflammation in iris tissues was the main pathological feature for uveitis, especially for uveitis at the active stage. Uveitis is known to be initiated by the recognition of T cells to retinal or cross-reactive antigens, and recruited inflammatory cells result in the damage of specific tissues. The inhibition of inflammation and immunosuppression has become the preferred therapeutic strategy for uveitis . Here, we observed the infiltration of inflammatory cells in iris tissues in 25% cases. This phenomenon indicated that patients with a quiet uveitis also have an activated inflammation in iris. Recurrent uveitis is mediated by autoaggressive Th response, which could be induced by dysregulated immune response and T cells infiltration . Therefore, the persistent inflammatory state in iris tissues may directly lead to the recurrence of uveitis after surgery in these cases. It is noteworthy that no recurrence of uveitis was revealed in these cases, except one case with ankylosing spondylitis. This phenomenon may directly attribute to the removal of pathological tissues. Surprisingly, although recurrent uveitis is characterized by a persistent inflammatory response, the inflammatory cell infiltration was not observed in the left 75% cases. It remains unclear why the inflammatory cells were disappeared somehow, and this is an urgent problem to be solved in future.