Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
Sugita Eye Hospital, Nagoya, Japan.
Ophthalmology. 2023 Jun;130(6):608-614. doi: 10.1016/j.ophtha.2023.01.016. Epub 2023 Feb 1.
To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD).
A prospective, multicenter, open-label, uncontrolled, single-arm clinical trial.
Ten consecutive eyes of 10 patients with unilateral LSCD were followed for 2 years after surgery. Preoperative LSCD stage was IIB in 4 eyes and III in 6 eyes.
A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed on by global consensus, with eyes evaluated as being in stages IA-C representing successful corneal epithelial reconstruction. Diagnosis and staging of LSCD were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised 2 or 3 third-party cornea specialists, who were provided with information anonymously and randomly.
Corneal epithelial reconstruction rate was the primary end point.
Corneal epithelial reconstruction was successful in 6 of 10 eyes (60%) 1 year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes 2 years postoperatively. Additionally, improvements in visual acuity were noted in 50% and 60% of eyes at 1 and 2 years, respectively. No clinically significant transplantation-related adverse events were observed.
The efficacy and safety of cultivated limbal epithelial cell sheet transplantation were thus confirmed, and the cell sheet, named "Nepic," is now approved as a cellular and tissue-based product in Japan.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
在符合政府监管临床试验的良好生产规范 (GMP) 的条件下，确认同种异体培养的角膜缘上皮细胞片治疗单侧角膜缘干细胞缺陷 (LSCD) 的疗效和安全性。
前瞻性、多中心、开放标签、非对照、单臂临床试验。
10 例单侧 LSCD 患者的 10 只眼，术后随访 2 年。4 只眼术前 LSCD 分期为 IIB 期，6 只眼为 III 期。
从健眼获取角膜缘组织活检，然后将角膜缘干细胞解离并在温度响应培养表面上培养。所有细胞片均在符合 GMP 标准的设施中，按照既定的标准操作程序制造。在移植前使用定义的运输标准评估细胞片，只有符合标准的细胞片才会被使用。在去除覆盖角膜表面的结膜瘢痕组织后，将细胞片移植到每位患者的病变眼中。根据全球共识达成的分期方法，根据角膜上皮重建的严重程度来判断 LSCD 的严重程度，IA-C 期的眼睛表示角膜上皮重建成功。LSCD 的诊断和分期由试验的入选判断委员会和效果评估委员会通过包括荧光素染色的裂隙灯照片进行判断。这两个委员会都由 2 或 3 名第三方角膜专家组成，他们匿名和随机地提供信息。
角膜上皮重建率为主要终点。
术后 1 年，10 只眼中有 6 只（60%）角膜上皮重建成功，明显高于同种异体角膜缘移植的 15%临床有效率。术后 2 年，重建率为 70%。此外，术后 1 年和 2 年分别有 50%和 60%的眼睛视力有所提高。未观察到与移植相关的有临床意义的不良事件。
因此，培养的角膜缘上皮细胞片移植的疗效和安全性得到了确认，该细胞片名为“Nepic”，现已在日本被批准为细胞和组织基产品。
