PURPOSE
To compare submandibular gland (SMG) transplantation with minor salivary gland (MSG) transplantation for the treatment of different dry eye diseases (DED).
DESIGN
Retrospective clinical cohort study.
METHODS
A total of 73 refractory DED eyes were divided into 3 groups. Group A comprised 35 end-stage DED eyes that underwent SMG transplantation. Group B comprised 20 end-stage DED eyes with MSG transplantation. Group C comprised 18 non−end-stage DED eyes with MSG transplantation. Schirmer test (ST), tear break-up time (TBUT), corneal fluorescein staining (FL), and best-corrected visual acuity (BCVA) were measured before and after surgery.
RESULTS
Hospital length of stay, length of operation, and hospital fee were significantly higher in group A than in group B or C. Eyes in group A showed the most severe DED disease, with preoperative ST, TBUT, FL, and BCVA of 0.36 mm per 5 minutes, 0.03 seconds, 10.97, and 0.11, respectively, which improved significantly to 20.23 mm per 5minutes, 1.74 seconds, 7.58, and 0.2 at >2-year follow-up. Group B had similar baseline data, and significant but limited improvement only in the ST (0.55 mm per 5 minutes to 3.79 mm per 5 minutes) and FL (11.10 to 9.58) after the operation. Group C had better baseline ST, TBUT, FL, and BCVA of 0.89 mm per 5min, 3.49 seconds, 1.83, and 0.81, respectively, which improved significantly (except for BCVA) to 9.35 mm per 5min, 9.08 s, 0.53, and 0.89 after MSG transplantation.
CONCLUSION
SMG transplantation could be recommended to treat end-stage refractory DED. MSG transplantation may provide satisfying results for refractory DED with relatively less severe impairment of the eye.
B ecause of its multifactorial etiology, the management of dry eye disease (DED) is complicated. Recently, the Tear Film and Ocular Surface Society’s Dry Eye Workshop II (TFOS DEWS II) proposed an evidence-based, multi-staged management algorithm to determine the most appropriate DED treatment for each patient. The treatment is recommended based on subjective and objective severity measurements. Health education, environmental modifications, ocular lubricants, tear conservation, and physical therapies are recommended first. When the above options are insufficient, prescription drugs, autologous/allogeneic serum eye drops, and therapeutic contact lenses are recommended. Surgeries are usually given for refractory DED. Two surgical modalities of salivary gland transplantation, microvascular submandibular gland (SMG) transplantation and minor salivary gland (MSG) transplantation, are listed as the last recommendations when other treatments are inadequate. However, further instruction on choosing between these 2 surgical approaches is still vague.
Both SMG transplantation and MSG transplantation provide spontaneous, continuous, and endogenous lubrication with saliva as a tear substitute. Both treatments can improve severe symptoms and/or signs of dry eye, including Schirmer test score (ST), tear break-up time (TBUT), and some other ocular surface features. However, despite the above-listed similarities, these methods differ in surgical complexity or technical requirement, surgical trauma, secretory patterns, amounts of lubrication, and surgical complications. Besides, there is individual heterogeneity among these refractory DED patients, and the etiology and severity of the disease in these patients may vary. Taking into consideration significant differences between the 2 surgeries and the heterogeneity among the refractory DED patients, when salivary gland transplantation is indicated according to the current algorithm, an evidence-based choice between SMG transplantation and MSG transplantation is needed.
In this study, we compared the treatment effect of SMG transplantation and MSG transplantation in different refractory DED patients. We also analyzed surgical complications and treatment costs. The current study provides evidence-based indications for SMG transplantation and MSG transplantation for the treatment of severe refractory DED.
METHODS
PATIENTS
Consecutive patients diagnosed with DED who underwent salivary gland transplantation at Peking University School of Stomatology between June 2010 and October 2018 were included in this retrospective clinical cohort study. The study was approved by the Ethics Committee of the Peking University School of Stomatology (PKUSSIRB – 202163043) and designed and carried out in full accordance with the World Medical Association Declaration of Helsinki. All patients provided informed consent to join the study.
INDICATIONS AND CONTRAINDICATIONS
Indications for surgeries included persistently pronounced symptoms of dry eye and failure of other previous ophthalmologic treatments, along with an ST value of <2 mm, a TBUT value of <5 seconds, and positive fluorescence staining of the cornea during ophthalmologic evaluation. Contraindications were Sjogren syndrome or obvious symptoms of xerostomia. ,
GROUPING
Patients comprised 3 groups (groups A, B, and C) based on their surgical modalities, the severity of DED, and the etiologies of the DED ( Table 1 ). Group A comprised DED patients secondary to cicatrizing conjunctivitis and meeting the level 4 grade of dry eye severity grading scheme in the 2007 International Dry Eye WorkShop (DEWS) criteria who underwent SMG transplantation. Group B comprised level 4 DED patients secondary to cicatrizing conjunctivitis who underwent MSG transplantation. Group C comprised the DED patients with secondary to non-cicatrizing conjunctivitis who did not meet the level-4 grade in the DEWS criteria. The surgical modality was selected mainly according to the patient’s intention after surgical techniques had been explained in detail.
| Characteristics | Group A | Group B | Group C | P Value | ||
|---|---|---|---|---|---|---|
| A vs B | B vs C | |||||
| Grouping methods | DED etiology | Cicatrizing conjunctivitis | Cicatrizing conjunctivitis | Non-cicatrizing conjunctivitis | ||
| DED severity level | Level 4 | Level 4 | Level <4 | |||
| Surgical modality | SMG transplantation | MSG transplantation | MSG transplantation | |||
| Numbers | Patients | 28 | 19 | 14 | ||
| Eyes | 35 | 20 | 18 | |||
| Patients with bilateral surgeries | 7 (25%) | 1 (5.3%) | 4 (28.6%) | .119 | .138 | |
| Demographic features | Age (y) | 29.6 ± 15.1 | 34.4 ± 10.5 | 28.2 ± 4.2 | .211 | .022 |
| Sex (female/male) | 23/12 | 12/8 | 4/14 | .672 | .019 | |
| Disease history | Detailed etiology | SJS: 35 | SJS: 17 GVHD: 3 | AC: 13 Unknown: 5 | ||
| Disease duration (y) | 11.3 ± 11.6 | 10.5 ± 9.1 | 5.1 ± 3.2 | .781 | .020 | |
| Hospital parameters | LOS (day) | 13.0 ± 1.1 | 7.8 ± 0.7 | 7.5 ± 0.7 | <.001 | .287 |
| LOO (h) | 6.1 ± 0.6 | 1.9 ± 0.3 | 1.8 ± 0.3 | <.001 | .310 | |
| Hospital fee (RMB) | 28486.2 ± 2740.0 | 16006.7 ± 2217.6 | 16845.6 ± 3617.6 | <.001 | .389 | |
| Donor parameters (MSG) | Donor sites | —— | Lower lip: 14 Upper lip: 5 Buccal: 1 | Lower lip: 13 Upper lip: 5 Buccal: 0 | .627 | |
| Sizes (cm 2 ) | —— | 8.8 ± 2.5 | 6.6 ± 1.6 | .003 | ||
| MSGFR (mg/min) | —— | 1.8 ± 0.6 | 3.2 ± 1.1 | <.001 | ||
| Size × MSGFR | —— | 15.9 ± 6.5 | 21.1 ± 8.2 | .045 | ||
The causes of cicatrizing conjunctivitis included Stevens−Johnson syndrome (SJS), mucous membrane pemphigoid (MMP), and graft-versus-host disease. Based on the DEWS dry eye severity grading scheme, the inclusion criteria for level 4 DED were as follows: (1) severe constant discomfort of the eye and (2) constant visual diminution affecting the lifestyle; (3) corneal fluorescein staining (FL) score >6 in a standardized scoring scheme with a maximum score of 12; (4) TBUT ≤1 second; and (5) ST ≤2 mm per 5 min.
TRANSPLANTATION PROCEDURES FOR MICROVASCULAR SUBMANDIBULAR AND MINOR SALIVARY GLANDS
SMG transplantation was performed as previously described ( Figure 1 ). In brief, under general anesthesia, the SMG, including the branches of facial artery and vein and Wharton duct, was harvested from the submandibular triangle and transferred to the temporal region. The branches of the vessels from or going into the SMG had to be harvested together. Next, the facial artery and facial veins were subjected to anastomosis with the superficial temporal artery and vein, respectively. After subcutaneously passing through a tunnel prepared to the upper lateral conjunctival fornix, the distal end of the Wharton duct was sutured in the upper lateral conjunctival fold as an opening.
The MSG transplantation was performed as previously described ( Figure 2 ). Before surgery, the minor salivary gland flow rate (MSGFR) of 3 sites (upper labial, lower labial, and buccal mucosa) was measured and calculated as previously described. , The lower or upper labial glands with higher flow rates were used as the donor sites. In cases in which the flow rate of upper and lower labial glands was much lower than that of the buccal glands, the latter was used as a donor. Under general anesthesia, the graft was obtained from the donor bed and composed of salivary lobules and the covering mucosa. The recipient beds were prepared in the upper and lower bulbar conjunctiva and near the fornix. The graft’s mucosa was covered by 8-0 Vicryl absorbable sutures and anchored to the underlying orbital septum with 1 interrupted suture passing through the donor tissue to achieve good contact between the graft and the graft underlying recipient bed. No other compression methods were used.
