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Limbal stem cell deficiency (LSCD) is an ocular surface disease resulting from a reduction and/or dysfunction of limbal stem cells. The symptoms of LSCD are non-specific and can be difficult to distinguish from other ocular surface diseases through slit-lamp examination. Impression cytology is currently considered the gold standard for LSCD diagnosis; however,it is a qualitative method with low sensitivity. Nonetheless,emerging imaging techniques offer quantitative diagnosis and staging of LSCD. This review article examines four imaging methods and their associated parameters for diagnosing LSCD: optical coherence tomography,which measures corneal epithelial thickness; optical coherence tomography angiography,which detects corneal neovascularization; in vivo confocal microscopy,which measures corneal epithelial thickness,subbasal nerve density,and corneal basal cell density; and future applications of full-field/spectral-domain optical coherence tomography.

Objective: To analyze the clinical features and treatment outcomes of eyes with contact lens-induced limbal stem cell deficiency (CL-iLSCD). Methods: This cross-sectional study involved patients diagnosed with CL-iLSCD at the Eye, Ear, Nose & Throat Hospital of Fudan University between October 2018 and September 2022. A total of 17 patients (25 eyes) with a mean age of (36.4±6.9) years were enrolled. Among them, 14 were females (82.4%). Corneal and limbal abnormalities, especially the range of epitheliopathy, were observed under a slit lamp biomicroscope with fluorescein staining. Anterior segment optical coherence tomography and in vivo laser scanning confocal microscopy were performed to obtain the central corneal epithelial thickness, density of basal epithelial cells and corneal nerve fiber length. The clinical features of CL-iLSCD, along with their treatment outcomes and related risk factors, were analyzed. Results: All patients wore soft contact lenses, with an average daily wearing time of (10.5±2.5) hours and a median wearing duration of 10 (4 to 30) years. Ocular symptoms, including decreased vision, ocular discomfort or pain, redness, and photophobia, were present in 22 eyes (88.0%). The most characteristic clinical sign of CL-iLSCD was comb-or whorl-pattern late fluorescein staining under cobalt blue light, which was most commonly seen at the superior limbus (25/25, 100.0%). Additionally, reductions in central corneal epithelial thickness, basal cell density, and corneal nerve fiber length were observed. A comprehensive score was assigned to each eye based on clinical findings and in vivo imaging biomarkers. LSCD was mild, moderate, and severe in 5, 11, and 8 eyes, respectively. A history of misdiagnosis was found in 20 eyes (80.0%). After discontinuing the use of contact lenses and receiving medical treatment, significant improvement was observed in all eyes, with 13 eyes fully recovered. Conclusions: The symptoms and clinical signs of CL-iLSCD can be subtle at the early stage. Discontinuing contact lens wear and medication are effective to treat CL-iLSCD.

The 31-year-old female patient was admitted to the General Hospital of the Chinese People's Liberation Army for 3 days after the corneal transplantation of her right eye for 5 months.Four years ago, the patient developed red eyes, pain, dryness and photophobia after intravenous drip of cefuroxime sodium and metronidazole due to pelvic inflammation, accompanied by high fever, systemic rash and epidermal exfoliation, fingernail peeling, and mucosal ulceration in the eyes and mouth.Later, the patient received systemic hormone shock and point eye treatment in a local hospital, and the dry eyes gradually worsened. Despite continuous artificial tears and bandage mirror treatment, the corneal ulcer perforation in both eyes still occurred successively. After several penetrating keratografts and drug therapy, the ulcer and dissolution could not be prevented. He was admitted to our hospital due to corneal perforation in both eyes.Ophthalmic examination: visual acuity manual/15 cm in the right eye, intraocular pressure T-2, conjunctival sac stenosis, extensive corneal opacity and edema, ulcer about 8 mm, corneal perforation near the corneal limbus about 2 mm×5 mm below.The left eye had no light perception, a central corneal ulcer of about 8 mm, bulge of the posterior elastic layer, no anterior chamber, and atrophy of the eyeball.B-ultrasound showed choroidal detachment of the right eye.On the second day, the patient received right eye intraocular exploration, vitrectomy, ecotopic keratoscleral carrier Boston Ⅱ artificial keratoplasty, glaucoma valve implantation, autogenous ear cartilage implantation, conjunctival occlusion, and left eye lamellar keratoplasty, conjunctival occlusion.Postoperative visual acuity of right eye was -6.50 DS=0.12, intraocular pressure TN, ocular surface was stable.The left eye has no light perception and the ocular surface is stable.

Limbal stem cell deficiency is an ocular surface disease with the imbalance of corneal epithelial homeostasis caused by decrease of number or weakening of function of limbal stem cells. In 2019 and 2020, the international limbal stem cell deficiency working group developed and released the international consensus on the definition, classification, diagnosis, staging and management of limbal stem cell deficiency, which provided a standard protocol for related research and clinical diagnosis and treatment of limbal stem cell deficiency. In order to help Chinese ophthalmologists to properly understand its core components, there is a need to make in-depth interpretation to the key and difficult contents of the international consensus . (Chin J Ophthalmol, 2021, 57: 95-99) .

Limbal Stem Cell Deficiency (LSCD) is an ocular surface disease caused by the decrease of the quantity and dysfunction of limbal stem cell, which is characterized by conjunctivalization and other signs of epithelial dysfunction. For sever LSCD, surgery is the main treatment way. Recently, plenty of researches published the outcomes of different operation methods. This article summarized five major operations, including conjunctival limbal autograft (CLAU), simple limbal epithelial transplantation (SLET), limbal allograft, cultivated limbal stem cell transplantation (CLET) and cultivated oral mucosal epithelial transplantation (COMET). (Chin J Ophthalmol, 2020, 56:956-960) .

Objective: To investigate the cellular changes and quantitative analysis of basal cell density (BCD) and corneal epithelial thickness (CET) in limbal stem cell deficiency (LSCD) by in vivo confocal microscopy (IVCM). Methods: Prospective case-control study. A total of 35 eyes of 23 patients diagnosed with LSCD and 25 eyes from normal subjects were included in this study. Based on slit-lamp presentation and the global consensus on classification, the LSCD patients were classified into LSCD Ⅰ, LSCD Ⅱ and LSCD Ⅲ. Confocal images of the central cornea, and the superior, inferior, nasal and temporal limbus were inspected by IVCM. Morphologic characteristics of LSCD were summarized. The BCD and CET in all locations were measured. ANVOA or Kruskal-Wallis test was used for analysis when appropriate. A receiver operating characteristic was used to detect the diagnosis efficiency of BCD and CET. Results: The characteristics in the corneal epithelium of LSCD on IVCM included nested corneal epithelial cells, goblet cells with hyper-reflective spots, irregular basal cells and decreasing subbasal nerve density. The mean BCD of the LSCD group was (8 976±1 096) cells/mm 2 in the central cornea. Compared to the control group, the BCD in the central cornea, superior, inferior, nasal and temporal limbus decreased by 30.2%, 26.0%, 28.7%, 29.3% and 30.2%, respectively (all P <0.007). The CET in the central cornea was (47.3±8.1) μm. The CET in the central cornea, superior, inferior, nasal and temporal limbus decreased by 27.9%, 23.7%, 20.6%, 26.9% and 23.1%, respectively, compared to the control group (all P <0.007). There was a decline of BCD and CET in more serious LSCD. Additionally, the decline of BCD and CET was shown in the unaffected region. The receiver operating characteristic showed the diagnosis efficiency of BCD in the corneal center and limbus (0.931 and 0.916) was superior to CET (0.853 and 0.817). Conclusions: There was a series of characteristic cellular changes in LSCD on IVCM. Both BCD and CET decreased significantly in LSCD. The BCD had higher diagnostic efficiency for LSCD. (Chin J Ophthalmol, 2020, 56:447-455) .

Objective: Introduce the surgical techniques of bridge-shaped flap penetrating keratoplasty and whole lamellar keratoplasty with corneoscleral limbal and the comparison of therapeutic effects on keratoglobus. Methods: Five patients (eight eyes) with keratoglobus from January 2010 to December 2015 were included. Three eyes received bridge-shaped flap penetrating keratoplasty (two eyes with corneal penetrating injury due to trauma, one eye with descemet's membrane detachment) and five eyes received whole lamellar keratoplasty with corneoscleral limbal. Results: The patients (four male, one female) aged 3 to 67 years old. Three younger patients were complicated with blue sclera. The visual acuity of all the patients pre-operation were lower than 0.05. The average visual acuity after whole lamellar keratoplasty (LKP) surgery was 0.2, while the average visual acuity after bridge-shaped flap penetrating keratoplasty (PKP) was 0.5. The corneal epithelium of the three eyes received bridge-shaped flap PKP surgery was completely healed within a week with no recurrence of corneal epithelial defect. Whereas one eye after whole LKP surgery arised persistent corneal epithelial defect and healed after blepharorrhaphy. The corneal epithelial of another eye after whole LKP surgery healed slowly and was completely healed after wearing a bandage lens on corneal for 2 months. The corneal epithelial of the remaining three eyes after whole LKP surgery was completely healed within a week. Two eyes received bridge-shaped flap PKP surgery arised corneal graft rejection 2 months after operation and recovered after anti-rejection treatment. No corneal graft rejection arised in the patients receiving whole LKP surgery. Conclusions: The whole lamellar keratoplasty with corneoscleral limbal could effectively reinforce corneal, avoid corneal penetrating injury caused by minor trauma, and improve visual acuity in keratoglobus whose corneas were gradually thinning and corrected vision cannot be improved. The patients with corneal perforating injury or descemet's membrane detachment could obtain good visual prognosis receiving bridge-shaped flap penetrating keratoplasty. (Chin J Ophthalmol, 2019, 55:916-922) .

Objective: To determine the safe distance range of clear corneal incision (CCI) from the corneal limbus and how different CCI sites affect surgery efficacy and anterior segment parameters in patients undergoing phacoemulsification., Methods: This retrospective case-control study was conducted in 44 patients (44 eyes) undergoing phacoemulsification and IOL implantation. The patients were divided into two groups with CCI distances ranging from 1 mm to 1.5 mm (group A, n = 22) and from 0.5 mm to 1.0 mm (group B, n = 22). The visual acuity, surgically induced astigmatism (SIA), corneal aberration, and anterior segment parameters were analyzed., Results: Compared with the preoperative data, all the patients showed significant improvements in the postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), anterior chamber depth (ACD), and anterior chamber angle (ACA) after the surgery ( P &lt; 0.05). No significant differences were found between the two groups in postoperative UCVA, BCVA, SIA, total corneal aberration RMS, lower- and higher-order aberration RMS, spherical aberration (Z 4 0 ), horizontal three leaf clover (Z 3 3 ), vertical three leaf clover(Z 3 -3 ), horizontal coma(Z 3 1 ), vertical coma(Z 3 -1 ), ACD, ACA, anterior chamber volume, or central corneal thickness ( P &gt;0.05)., Conclusions: Phacoemulsification is an effective therapy for cataract with a CCI distance range either of 1-1.5 mm or 0.5-1.0 mm. These two CCI distance ranges produce no significant differences in the visual quality following phacoemulsification, indicating that a CCI distance range of 0.5-1.5 mm can be safe for phacoemulsification.

Ocular chemical burns are common and serious ocular emergencies which require immediate and intensive evaluation and treatment. Loss of vision and disfigurement affect the victims, bringing great sufferings to themselves and their families. China is the biggest developing country in the world with a large number of such cases. The prevention of ocular chemical burns is emphasized in different aspects. After emergency treatment, proper care of chemical burns is started by control of inflammation with corticosteroids. Topical and systemic ascorbic acid supplement is important. Re-epithelialization is critical to stabilize the ocular surface and to prevent corneal ulceration and melting. The goal of treatment is mainly to restore the ocular structure and function. Neuroprotection is important during the treatment course for control of both glaucoma and inflammation. Prognosis depends on the degree of limbal, corneal and conjunctival involvement at the time of injury as well as the management. Medical treatments only or with combination of surgical procedures, including amniotic membrane transplantation, epithelial or limbal stem cell transplantation, tenonplasty, keratoplasty and keratoprosthesis, are according to the classification of ocular chemical burns and the phases. Further investigations should be done in the future in both prevention and management of ocular chemical burns in China. (Chin J Ophthalmol, 2018, 54: 401-405 ) .

Objective: To introduce the surgical methods and investigate the treatment effects of conjunctival lesion resection combined with transplantation of allogeneic limbal epithelia cultured in vitro for treatment of varied large conjunctival lesions. Methods: A retrospective analysis of case data of the patients receiving transplantation of allogeneic limbal epithelia cultured in vitro for large conjunctival lesions at Qingdao Eye Hospital from January 2013 to December 2015 was conducted. Fresh donor corneal limbal epithelial tissues were obtained for cellular digestion and isolation. The cells were cultured on de-epithelized amniotic membrane to form a stratified cell sheet with 3 to 5 layers of cells for reservation. Conjunctival lesions were removed, and corneal limbal epithelial cell sheets corresponding to the size of the conjunctival defects were covered on the scleral flaps, before the conjunctivae were para sutured with corneal limbal epithelial cell sheets. The stitches were removed 7 days after surgery. The treatment effects were evaluated. Results: There were 11 cases (12 eyes) in this study, including 6 cases (6 eyes) of recurrent pterygium combined with symblepharon, 3 cases (3 eyes) of conjunctival compound nevus, 1 case (1 eye) of conjunctival primary acquired melanosis, and 1 case (2 eyes) of dermoid lipoma. The patients were 6 to 69 years old, with an average age of (46±23) years old. There were 5 male patients and 6 female patients. The follow-up time was 6 to 39 months, with an average time of (24.8±12.4) months. The conjunctival lesions in all patients were more than 2 quadrants. No patients had intraoperative and postoperative complications. No obvious irritation symptoms were observed after surgery. There were a few small pieces of epithelial defects on the limbal epithelial cell sheets at the end of the operation due to operative injury. With postoperative cellular proliferation and repair, the epithelium gradually healed and tended to become firm, and the boundaries with original conjunctival epithelium gradually disappeared. The healing time of the epithelium after surgery was 3 to 7 days, with an average time of (4.5±1.2) days. No immunological rejection occurred after surgery. No recurrence of original diseases was observed among all the patients at the last follow-up. Conclusions: Transplantation of allogeneic cultured limbal epithelial cells, which was carried out for the treatment of large conjunctival lesions, witnessed rapid epithelization at the areas of lesion resection. It could reduce the risk of recurrence of original diseases and effectively avoid the occurrence of postoperative symblepharon. The postoperative inflammatory reaction was also minor. (Chin J Ophthalmol, 2017, 53:172-176) .

Objective: To evaluate the application of anterior segment optical coherence tomography (ASOCT) in surgical design for residual horizontal strabismus patients., Methods: This article was a retrospective case series analysis. Total 20 residual strabismus patients (13 with residual exotropia and 7 with residual esotropia) in Eye Hospital of Wenzhou Medical University from Jan 2009 to Jan 2011 were studied. Routine strabismus examinations were completed preoperatively. The distance between insertion of horizontal rectus muscles and corneal limbus were measured with ASOCT preoperatively and calipers intraoperatively. Reoperational amount and method for residual strabismus patients were designed according to the limbus-insertion distance. The paired t test was used to compare the agreement between two methods of measurement of limbus-insertion distance. The cure rates of reoperation were analyzed., Results: No statistical significance was observed between the measurements with ASOCT (7.7±1.7) mm and calipers (7.8±1.1)mm (t=-1.37, P=0.19). According to ASOCT image, the second surgical method was re-recession muscle for 4 patients; re-recession of original performed muscle combined with antagonist muscle resection for 10 patients and antagonist muscle resection combined with horizontal rectus muscle recession in fellow eye for 6 patients. All the surgical processes went on successfully, no severe intraoperative and postopereative complications were noted. Sixteen cases were cured (80%) ., Conclusions: Horizontal rectus muscle evaluation with ASOCT preoperatively may benefit the choice of performed muscle, calculation of surgical amount, reduction of unnecessary surgical procedure and optimization second surgical design for residual strabismus patients. (Chin J Ophthalmol, 2016, 52: 568-573).

Objective: To evaluate the change of corneal epithelial thickness after pterygium excision with conjunctival autograft transplantation by Fourier Domain Optical Coherence Tomography (FD-OCT) ., Methods: Twenty-two patients (24 eyes) with the diagnosis of primary pterygium were enrolled. They underwent pterygium excision combined with conjunctival autograft transplantation. Twenty-five volunteers (25 eyes) served as the normal control group. FD-OCT was performed preoperatively and 1, 2, 3, 5, 7 days postoperatively to measure the thickness of corneal epithelium at 1 mm and 2 mm anterior to the nasal or temporal scleral spur. Corneal fluorescein staining was performed simultaneously. Comparisons on the thickness of corneal epithelium were made between preoperative values and postoperative ones., Results: The thickness of cornea epithelium at 1 mm anterior to the scleral spur was (43.81 ± 2.55) µm in normal subjects. At day 1 after surgery, corneal epithelial thickness at the same location was (21.28 ± 5.72) µm and then gradually increased to (39.94 ± 5.47) µm at day 7 postoperatively. All the difference on postoperative days had statistically significant (t = -17.69, -14.97, -10.63, -9.86, -3.15, P < 0.05) . The thickness of cornea epithelium at 2 mm anterior to the scleral spur was (40.50 ± 3.17) µm in normal subjects. At day 1 after surgery, corneal epithelial thickness at the same location was (24.02 ± 5.92) µm, and then gradually increased to (940.34 ± 5.69) µm at day 7 postoperatively. All the difference on postoperative days except day 7 had statistically significant (t = -12.08, -10.27, -6.18, -2.99, P < 0.05). Cornea epithelium at this location repaired sooner than that at 1 mm anterior to the scleral spur. At day 1 after surgery, corneal epithelium defect area were (39.31 ± 22.77) mm(2), and then decreased to (1.01 ± 1.72) mm(2) at 7 days (t = 6.68, 5.55, P < 0.05). At day 7 postoperative, 66.7% patients had a complete recovery of corneal epithelium with no fluorescein staining., Conclusions: FD-OCT was the effective instrument for observing the change of limbus-peripheral cornea epithelium thickness.Within 7 days postoperatively, cornea epithelium restored almost normal. After pterygium surgery, limbus-peripheral cornea epithelium restoration showed the tendency from the central to peripheral cornea.

Objective: To evaluate the effect of ocular surface disease treated by limbal transplantation., Methods: In a prospective study, 5l eyes of 50 patients were treated with three kinds of surgical techniques: first, conjunctival limbal autograft (CLAU) transplantation; second, corneal lamellar allograft combined with limbal autograft transplantation and third, corneal lamellar allograft combined with limbal allograft transplantation. Their effects were evaluated., Results: All of the 18 patients of CLAU group were cured. The second surgical technique resulted in restoration of a stable ocular surface in 19 of 20 cases. 10 patients' visual acuities were improved two or more than two lines. 13 eyes of 12 patients were treated with the third surgical technique, resulting in graft ulceration in 4 patients and graft rejection in 4 patients with bad prognosis., Conclusions: The effect of unilateral ocular surface disease treated with limbal autograft transplantation is satisfactory. For bilateral ocular surface disease, the method of limbal allograft transplantation should be improved to resolve some problems such as graft rejection.

Purpose: To improve the prognosis of grafts for obsolete ocular chemical or thermal burns., Methods: LT + PK or PK were performed in 28 eyes with severe chemical or thermal burns. The effects of the two groups were compared., Results: In LT + PK group(12 eyes), during 5 to 28 months of follow-up, the results showed improved visual acuity in 9 eyes (75%), maintained stable epithelial adhesion without recurrent erosion or persistent epithelial defect in 11 eyes (91.67%), graft transparent in 9 eyes (75%). Nine eyes (75%) showed prevented neovascularization and conjunctival tissue from growing into graft. Allograft rejection were identified in 4 eyes (33.33%). In routine PK group (16 eyes), during 3 to 22 months of follow-up, the results showed improved visual acuity in 4 eyes (25%), maintained stable epithelial adhesion without recurrent erosion or PCED in 8 eyes (50%), graft transparent in 4 eyes (25%). Four eyes (25%) showed prevented neovascularization and conjunctival tissue from growing into cornea., Conclusions: Combined procedure of LT and PK is an effective treatment for severe ocular chemical or thermal burns. It can reduce persistent corneal epithelial defect and prevent neovascularization and conjunctival epithelial from growing into cornea thus maintaining graft transparent and improving visual acuity.

Objectives: To understand the clinical significance of corneal limbus transplantation on alkali burns., Methods: 14 New Zealand rabbits were used, 1.0 mol/L NaOH solution was placed on the anterior surface of the eyes for 1 minute. Limbal autograft transplantation was performed on 7 rabbits immediately after the burn. The other 7 rabbits were used as controls. The follow-up period lasted for 1 month and then the histopathological changes of corneas were observed under light and scanning electron microscopes., Results: Faster corneal epithelial healing, less corneal neovascularization and inflammatory cell infiltration occurred in the operative group., Conclusions: Early limbal autograft transplantation can accelerate corneal epithelial healing, restrain corneal neovascularization and inflammatory response, therefore it can prevent corneal ulceration.

Objective: To study the pathological diagnostic significance of argentophil protein (AgNOR) quantitative analysis at nucleolus area of limbus epithelial neoplasms., Methods: Automatic image analysis system was used for argentophil protein granule measurement in the pathologic diagnosis of 45 cases with limbus epithelial neoplasms, including benign hyperplasia, atypical hyperplasia, carcinoma in situ and squamous cell carcinoma., Results: In various lesions, there were the differences in the distributive pattern, size and area of AgNOR granules, which were closely related to the nature of the neoplasms (benign or malignant) and its cell differentiation., Conclusion: Automatic image analysis of AgNOR quantitative measurement on limbus epithelial neoplasms may indicate the proliferative activity and cell differentiation in various lesions, help to differentiate benign or malignant neoplasms and effectively enhance the level of pathologic diagnosis.