Sutureless contact lens-type amniotic membrane for persistent epithelial defects after infectious keratitis

Dear Editor,

We are writing to present two case reports of persistent epithelial defect after infectious keratitis successfully treated with sutureless contact lens-type amniotic membrane(AM) transplantation. Infectious keratitis is one of the leading causes of corneal blindness. Infection disrupts the normal corneal healing process and induces inflammation, limbal cell dysfunction, and corneal surface irregularity, which can lead to corneal opacities or persistent epithelial defects (PEDs)

.Untreated PED can cause corneal thinning, resulting in corneal perforation.

The AM has been used successfully to treat PED and ulcers from different pathologies

. AM transplantation (AMT) has been shown to effectively suppress inflammation and promote epithelial healing in intractable infectious keratitis. Therefore,performing AMT can prevent perforation and reduce the possibility of further surgical procedures, such as tectonic keratoplasty. However, AM is generally secured with surgical suturing. The disadvantages of sutures include prolonged surgical time, postoperative discomfort, and the risk of inflammation or infection

. Recently, sutureless contact lenstype AM has been introduced to overcome these drawbacks.Here, we report two infectious keratitis patients who had PED treated with the sutureless contact lens type of AMT.This study was conducted following the tenets set forth in the Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Hospital (No.2012-138-118).

In this case report, we used a newly developed 2MD10 (MS Bio Inc., Seongnam, Republic of Korea)consisting of two or three layers of AM. It is physically molded and non-chemically crosslinked to obtain a similar base curvature of a bandage soft contact lens and requires cryopreservation (Figure 1). Two patients with PED due to bacterial and neurotrophic keratopathy or

keratitis (AK) were treated with 2MD10 in 2020. Both patients achieved complete re-epithelialization without additional complications due to AMT.

A 70-year-old male was referred to our clinic with an intractable corneal ulcer that lasted more than 1mo. The patient reported left ocular pain with decreased vision that had developed 3mo previously. On initial examination, his visual acuity was a finger count in his left eye. The left eye showed a 6 (horizontal) ×3.5 (vertical) mm

corneal epithelial defect with inferior stromal infiltration, 360-degree corneal neovascularization, and mild anterior chamber reaction. PED secondary to infectious keratitis with neurotrophic keratopathy was suspected. Cultures of corneal scrapings were performed.The patient was subsequently started on empirical antibiotic therapy, including topical fortified vancomycin (2.5%) and ceftazidime (5%) every 2h. Corneal scrape cultures were positive for

species. Five days after treatment, the left ocular pain subsided, and corneal stromal infiltration and anterior chamber reaction decreased. However, corneal epithelial defects remained unchanged (Figure 2A and 2B).Topical medications were tapered four times a day, and sutureless contact lens-type AM (2MD10) was applied (Figure 2C). The AM was well positioned under the bandaged soft contact lens during the follow-up. Seven days later, the AM dissolved, and the corneal epithelial defect completely healed without the aggravation of infection (Figure 2D-2F).

A 69-year-old female was referred to our clinic for intractable infectious keratitis. The patient reported right ocular pain that developed after rubbing her eyes while gardening 15d prior. On initial presentation, the visual acuity was hand motion in the right eye. The right eye showed severe diffuse conjunctival injection, total corneal epithelial defect with paracentral ring infiltrates, severe corneal stromal edema,and a 3 mm hypopyon in the anterior chamber. Cultures from corneal scrapings showed

trophozoites and cysts (Figure 2G). The polymerase chain reaction (PCR)results for

were also positive. The patient was prescribed topical polyhexamethylene biguanide (PHMB;0.02%) hourly and fortified voriconazole (1%) every 2h. After 50d, corneal stromal infiltration decreased and the hypopyon vanished. However, PED with progressive superotemporal stromal thinning was observed despite the use of a pressure patch, soft contact lenses, application of a therapeutic bandage,and reduction of topical medication to six times per day(Figure 2H-2J). To prevent perforation, sutureless AMT using contact lens-type AM (2MD10) was performed (Figure 2K).The AM was well positioned under the bandaged soft contact lens, and there was no aggravation of the infection noted during the follow-up. Eight days later, AM dissolved, and corneal epithelization progressed. After 4wk of AMT, corneal epithelialization was completed (Figure 2L).

The 2MD10 has a trapezoidal shape and has a curvature similar to that of a normal cornea and is less likely to dislocate.Additionally, the two holes in AMT act as drainage holes to prevent tear and blood build-up between the cornea and AMT,which would cause dislocation of AMT. Indeed, the 2MD10 AM remained in place until it melted away in both patients in this study. Although cryopreservation is required, it is ready to use after resting at room temperature for approximately 30min.It is a cost-effective (approximately $200), convenient, and effective office-based treatment that can be widely used to treat patients with PED.

Two types of AMs that do not require sutures have been previously introduced. One type is the AM surrounded by as conformer ring, such as ProKera (Biotissue, Miami, FL, USA).The other type is the disc type AM, such as AmbioDisk (IOP Ophthalmics Inc., Costa Mesa, CA, USA) and BioDOPTIX(Labtician Ophthalmics, Oakville, Ontario, Canada). AM surrounded by as conformer ring consists of a concave polycarbonate dual-ring fastened with a sheet of cryopreserved AM that conforms to the corneal and limbal surfaces like a contact lens. The major drawbacks are the cost and discomfort in the form of foreign body sensations caused by the contact of a rigid polycarbonate ring with the eye

. Disc type AM is a freeze-dried AM that does not require cryopreservation

.It can be hydrated with a sterile solution and easily placed in the office. However, it is flat and is not always in place under a bandage soft contact lens

.

比较两组满意程度；微量泵注入胰岛素治疗的依从性、复常血糖的时间、住院治疗时间；护理前后血糖空腹指标、餐后2 h指标的监测结果；低血糖、酮症酸中毒等不良事件的发生率。

AM has been used as a basement membrane substitute in patients with PEDs both with and without corneal ulceration

.It provides epidermal growth factor, bFGF, keratinocyte growth factor, TGF-α and TGF-β, hepatocyte growth factor,and nerve growth factor to the ocular surface, and promotes epithelialization and suppresses corneal inflammation and neovascularization

.

We showed complete epithelialization in patients with PED due to infectious keratitis caused by sutureless AMT. Patient 1 (case 1) had bacterial keratitis combined with neurotrophic keratopathy, and patient 2 (case 2) had an

infection. Since AMT is also effective in neurotrophic keratopathy, it seems that corneal epithelization in case 1 was relatively faster than in case 2

. AK led to severe corneal inflammation and often presented a progressive chronic course with a long period of remission

. In addition, topical PHMB 0.02%, can induce cellar toxicity

. However, we could not discontinue PHMB because of the potential risk of AK reactivation. For these reasons, it seems that corneal epithelialization was slower in case 2 than in case 1. In summary, in both cases, corneal epithelialization was promoted after sutureless AMT, and side effects, such as exacerbation of infection, were not observed.

（三）病原变异 根据国家有关科研机构对2011年1～5月对12个省份28个规模化猪场的560份腹泻样品，3 751份病料组织进行病毒和细菌分离，综合分析，认为传染性腹泻病毒不断变异，高病性的流行性性腹泻病毒是引起当前规模化猪场产房腹泻性疾病的主要原因，也同时存在PEDV、TGEV、RV两种或3种病原混合感染致病，还检出了Boca（博卡）病毒和Kobu病毒。

2) 运输时间.货物在运输时所消耗的时间长意味着货物占用资金的时间长，会导致货物成本的增加.通过降低运输时间可以吸引顾客，提高运营商(水上“巴士”)的市场份额[13].因此运输时间是影响货主选择路径的重要因素，主要包括节点间的运输时间及节点处中转时间.

句法视角下校园中庭流动景观空间塑造策略——以仲恺农业工程学院英东楼为例 罗星海 蔡 如2018/01 104

To the best of our knowledge, this is the first case report on the use of a sutureless contact lens type of AM that retains its own curvature. The sutureless contact lens type of AM can be a convenient and effective office-based treatment for PED with infectious keratitis. In the future, an interventional randomized controlled trial is needed to determine whether the contact lens-type AM have significant effect on epithelial healing.

ACKNOWLEDGEMENTS

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