Recent and Evolving Therapies in the Management of Endothelial Diseases.

Corneal endothelium is the innermost layer of the cornea which has both barrier and pump function and very important to maintain cornea clarity. Unlike epithelium, endothelium does not have regenerative potential; hence, endothelial damage or dysfunction could lead to corneal edema and visual impairment. Advanced corneal transplantation which involves selective replacement of dysfunctional endothelium has led to improved and faster visual rehabilitation. But in recent times, alternative therapies in the management of corneal edema and endothelial diseases have been reported. In this review, we aim to give a comprehensive review of various strategies for the management of corneal endothelial dysfunction in order to give treatment which is precisely tailored for each individual patient. A review of all peer-reviewed publications on novel strategies for the management of endothelial dysfunction was performed. The various approaches to the management of endothelial dysfunction are compared and discussed. Shortage of human donor corneas globally is fuelling the search for keratoplasty alternatives. Corneal endothelial dysfunction can be caused following surgery, laser or corneal endothelial dystrophies which could be amenable to treatment with pharmacological, biological intervention and reverse the endothelial dysfunction in the early stages of endothelial failure. Pharmacological and surgical intervention are helpful in cases of good peripheral endothelial cell reserve, and advanced cases of endothelial cell dysfunction can be targeted with cell culture therapies, gene therapy and artificial implant. Treatment strategies which target endothelial dysfunction, especially FECD in its early stages, and gene therapy are rapidly evolving. Therapies which delay endothelial keratoplasty also are evolving like DSO and need more studies of long-term follow-up and patient selection criteria.

Use of topical anaesthesia and peribulbar anaesthesia in Descemets membrane endothelial keratoplasty.

INTRODUCTION: In instances where peribulbar anaesthesia (PBA) cannot be used, Descemet membrane endothelial keratoplasty (DMEK) surgery can be performed under topical anaesthesia (TA). We evaluated subjective pain and post-operative outcomes of DMEK surgeries performed under PBA and TA. METHODS: Sixty pseudophakic patients without history of ocular comorbidities underwent DMEK surgery under either PBA or TA. PBA was performed with a single injection of 6 mL Prilocaine Hydrochloride 2% in combination with 1500 I.U. hyaluronidase. For TA, patients were given 0.4% Oxybuprocaine eye drops followed by a 2% Lidocain Hydrochloride-Gel and an intraoperative injection of a 2% Lidocaine Hydrochloride solution into the anterior chamber. All surgeries were performed by the same surgeon. Subjective pain was measured using a visual analog scale (VAS). Secondary outcomes (BCVA, duration of surgery, endothelial density, rebubbling rate) were recorded during a follow-up period of 3 months. RESULTS: The mean subjective pain of patients in the PBA group was 1.27 (95% CI 0.87-1.68) and 1.64 (95% CI 1.15-2.21) in the TA group. The mean duration of surgery was 402 s (95% CI 356-448) in the PBA group and 427 s (95% CI 371-483) in the TA group, p = 0.477. No major differences were observed in BCVA, endothelium density and rebubbling rate between the two groups. Anaesthesia-related side effects were more frequent in the PAB group than in the TA group. CONCLUSION: Although levels of subjective pain are lower under PBA than under TA, in selected patients without ocular comorbidities TA can achieve levels of pain acceptable for DMEK surgery.

Ubiquinol Supplementation of Donor Tissue Enhances Corneal Endothelial Cell Mitochondrial Respiration.

PURPOSE: To determine whether ubiquinol improves mitochondrial function and cell viability in human donor corneal endothelial cells during hypothermic corneal tissue storage. METHODS: Endothelial cell Descemet membrane tissues were treated with 10 µM ubiquinol, the reduced form of the antioxidant coenzyme Q10, for 5 days in Optisol-GS storage media before assaying for mitochondrial activity using extracellular flux analysis of oxygen consumption. In addition, endothelial cell Descemet membrane tissues were analyzed for cell viability using apoptosis and necrosis assays. Control tissues from mate corneas were treated with diluent only, and comparisons were analyzed for differences. RESULTS: A total of 13 donor corneal tissues with a mean (SEM) preservation time of 11.8 days (0.4) were included for the analysis. Treatment with 10 µM ubiquinol increased spare respiratory capacity by 174% (P = 0.001), maximal respiration by 93% (P = 0.003), and proton leak by 80% (P = 0.047) compared with controls. Cells treated with ubiquinol had no significant change in cell necrosis or apoptosis. CONCLUSIONS: Preliminary testing in donor corneal tissue at specified doses indicates that ubiquinol may be a useful biocompatible additive to hypothermic corneal storage media that increases corneal endothelial cell mitochondrial function. Additional investigations are indicated to further study and optimize the dose and formulation of ubiquinol for use in preserving donor corneal tissue function during hypothermic storage.

Dietary Melatonin Therapy Alleviates the Lamina Cribrosa Damages in Patients with Mild Cognitive Impairments: A Double-Blinded, Randomized Controlled Study.

BACKGROUND Alzheimer's disease (AD) is a degenerative disease that is characterized by massive neuron devastations in the hippocampus and cortex. Mild cognitive impairment (MCI) is the transitory stage between normality and AD dementia. This study aimed to investigate the melatonin induced effects on the lamina cribrosa thickness (LCT) of patients with MCI. MATERIAL AND METHODS The LCT data of patients with MCI were compared to LCT data of healthy controls. Subsequently, all MCI patients were randomly assigned into an experimental group (with melatonin treatment) or a placebo group (without any melatonin treatment). RESULTS The LCT of MCI patients decreased significantly compared with healthy controls. The univariate analysis showed that the lower the Mini Mental State Examination (MMSE) score (P=0.038; 95% CI: 0.876, -0.209), the smaller hippocampus volume (P=0.001; 95% CI: -1.594, -2.911), and the upregulated level of cerebrospinal fluid (CSF) T-tau (P=0.036; 95% CI: 2.546, -0.271) were associated significantly with the thinner LCT in MCI patients. There were 40 patients in the experimental group and 39 patients in the placebo group. The mean age of the experimental group was not significantly different from the placebo group (66.3±8.8 versus 66.5±8.3; P>0.05). The LCT and hippocampus volume of the melatonin treated group were significantly larger compared with the placebo group (P<0.001). On the other hand, the CSF T-tau level of the melatonin treated group was significantly lower compared with the untreated group (P<0.001). CONCLUSIONS LCT assessment might allow early diagnosis of MCI. Dietary melatonin therapy could provide an effective medication for MCI patients with LCT alterations.

Evaluation and Clinical Course of Keratomalacia With Descemetocele in a Child With Autism and Vitamin A Deficiency.

Autistic children with selective diets have an elevated risk for vitamin A deficiency. The authors present the case of a 7-year-old boy with keratomalacia resulting from dietary vitamin A deficiency. Optical coherence tomography and ultrasound biomicroscopy can provide useful details of the cornea and underlying structures. Vitamin A supplementation can result in significant resolution, obviating the need for surgical intervention. [J Pediatr Ophthalmol Strabismus. 2020;57:e1-e3.].

Corneal Stromal Edema during Lidocaine Injection for Blepharoplasty

PURPOSE: To report a case of corneal edema caused by an iatrogenic lidocaine injection into the corneal stroma created while performing a local anesthetic (lidocaine) injection into the eyelid for a blepharoplasty procedure. CASE SUMMARY: A 15-year-old female visited our clinic after the onset of severe pain and decreased visual acuity while receiving a local anesthetic injection in the upper blepharon for a blepharoplasty procedure. At the first clinical visit, visual acuity was hand motion and an accurate anterior chamber examination was difficult because of corneal edema. The Seidel test was negative. On corneal optical coherence tomography, the corneal thickness was 1,580 µm without any sign of Descemet's membrane detachment. We prescribed 5% NaCl four times a day and prednisolone acetate eight times a day. On the next day after injury, the corneal edema was significantly improved (central corneal thickness: 660 µm), and Descemet's membrane detachment was still not observed. One week after injury, the naïve visual acuity was 20/20, the central corneal thickness was 560 µm, and the endothelial cell count was 3,260 cells/cm². Three weeks after injury, the corneal edema was fully resolved and only slight temporal corneal haziness remained. After 2 months, the cornea was clear without any subjective discomfort. CONCLUSIONS: Corneal edema without Descemet's membrane detachment can be resolved spontaneously without aggressive treatment such as gas or air injection. However, endothelial cell count and corneal opacity need to be monitored on follow up exam. This clinical experience suggests that severe corneal edema in anterior stromal layer could be spontaneously resolved without severe complication.

Descemet's Membrane Biomimetic Microtopography Differentiates Human Mesenchymal Stem Cells Into Corneal Endothelial-Like Cells.

PURPOSE: Loss of corneal endothelial cells (CECs) bears disastrous consequences for the patient, including corneal clouding and blindness. Corneal transplantation is currently the only therapy for severe corneal disorders. However, the worldwide shortages of corneal donor material generate a strong demand for personalized stem cell-based alternative therapies. Because human mesenchymal stem cells are known to be sensitive to their mechanical environments, we investigated the mechanotransductive potential of Descemet membrane-like microtopography (DLT) to differentiate human mesenchymal stem cells into CEC-like cells. METHODS: Master molds with inverted DLT were produced by 2-photon lithography (2-PL). To measure the mechanotransductive potential of DLT, mesenchymal stem cells were cultivated on silicone or collagen imprints with DLT. Changes in morphology were imaged, and changes in gene expression of CEC typical genes such as zonula occludens (ZO-1), sodium/potassium (Na/K)-ATPase, paired-like homeodomain 2 (PITX2), and collagen 8 (COL-8) were measured with real-time polymerase chain reaction. At least immunofluorescence analysis has been conducted to confirm gene data on the protein level. RESULTS: Adhesion of MSCs to DLT molded in silicone and particularly in collagen initiates polygonal morphology and monolayer formation and enhances not only transcription of CEC typical genes such as ZO-1, Na/K-ATPase, PITX2, and COL-8 but also expression of the corresponding proteins. CONCLUSIONS: Artificial reproduction of Descemet membrane with respect to topography and similar stiffness offers a potential innovative way to bioengineer a functional CEC monolayer from autologous stem cells.

A Case of Descemet's Membrane Detachment during Lidocaine Injection for Hordeolum Incision and Drainage

PURPOSE: To report a case of Descemet's membrane detachment and corneal edema caused by an iatrogenic corneal perforation created while performing a local anesthetic (lidocaine) injection into the eyelid for a hordeolum incision and a drainage procedure. The detachment resolved after 14% C₃F₈ gas and air injections into the anterior chamber. CASE SUMMARY: An 8-year-old female visited our clinic after the onset of severe pain and decreased visual acuity while receiving a local anesthetic injection into the upper eyelid in preparation for a hordeolum incision and drainage procedure. Corneal optical coherence tomography (OCT) showed Descemet's membrane detachment. Three days after the first visit, the corneal epithelium had entirely healed. However, Descemet's membrane detachment persisted even after three weeks of follow-up. A corneal OCT was repeated after three weeks and showed a partial Descemet's membrane rupture. A more aggressive treatment method was deemed necessary, and gas and air injections into the anterior chamber were performed. After 48 hours, aside from some Descemet's membrane rolling at the site of rupture, overall reattachment of Descemet's membrane was noted. After three months of follow-up, the patient showed a stable corneal state and normalized vision. CONCLUSIONS: Descemet's membrane detachment and rupture resulting from an iatrogenic corneal perforation during an injection of lidocaine to the eyelid led to decreased visual acuity from corneal edema. As a more aggressive treatment method, 14 % C₃F₈ gas and air injections into the anterior chamber were performed and resulted in near complete reattachment of Descemet's membrane's and normalization of the patient's visual acuity.

Collagen cross-linking in recalcitrant corneal ulcers: A case series.

INTRODUCTION: Corneal ulcer is a leading cause of blindness worldwide. Many of these patients don't respond to conventional treatment with topical agents. Collagen cross-linking (CXL) has been suggested to avoid complications requiring emergency keratoplasty. SUBJECTS AND METHODS: Six eyes with presumed bacterial keratitis not responding to conventional treatment underwent CXL with ultraviolet A rays and transepithelial riboflavin. Patients with Descematocele and perforated ulcers were excluded. Preoperatively and postoperatively slit lamp examination of cornea and visual acuity recording was done. Postoperative outcome included subjective symptoms like relief in pain, photophobia, lacrimation and objective signs like improvement in epithelisation, corneal scarring with vascularisation. RESULTS: Four of the six eyes healed completely with scarring at 2 months follow-up. One of the patients developed Descematocele on 12 days which perforated later. Other patient developed Descematocele on 20 days post CXL. Of the subjective symptoms, pain and epiphora improved in all the patients except one. Photophobia improved only a week after CXL in four out of six patients. Epithelial defect completely healed over time in four out of six cases. All the cases who responded to treatment developed superficial and deep vascularisation of the cornea. Decrease in corneal edema and scarring was noted in four out of the six cases. CONCLUSION: The collagen cross-linking has a beneficial role as an adjuvant to medical therapy in recalcitrant bacterial keratitis. It helps in relief of pain and healing of ulcer. Larger randomized control trails with longer follow-up are required to come to a definite conclusion.

Agudeza visual y densidad de células endoteliales tras queratoplastia endotelial de membrana de Descemet (DMEK) / Visual acuity and endothelial cell density following Descemet membrane endothelial keratoplasty (dmek)

Objetivo: Evaluación de los resultados visuales y de la densidad de células endoteliales en los 120 primeros ojos sometidos a queratoplastia endotelial de membrana de Descemet (DMEK) como tratamiento para la distrofia endotelial de Fuchs. Material y métodos: Se evaluaron los primeros 120 ojos sometidos a DMEK. En todos ellos se midió la agudeza visual mejor corregida (AVMC) antes y al 1, 3 y 6 meses después de la cirugía, así como la densidad celular endotelial (DCE) antes y a los 6 meses. Resultados: En los ojos con trasplante exitoso y sin patologías concomitantes (n=96), se observo una AVMC en el 77% de los casos al mes de la cirugía, en el 92% a los 3 meses y en el 95% a los 6 meses. La AVMC fue mayor o igual 0,8 en el 50%, 63% y 73% de los casos y mayor o igual 1,0 en el 23%, 34% y 45% al 1, 3 y 6 meses después de la cirugía, respectivamente. La DCE preoperatoria fue 2.610 (más menos,185) células/mm2 y 1.770 (más menos, 520) células/mm2 a los 6 meses postcirugía. En quince ojos se realizó una queratoplastia endotelial con pelado de la membrana de Descemet (DSEK) secundaria. En este grupo, el 91% de los pacientes alcanzó una AVMC mayor o igual 0,5, alcanzando solo uno de ellos una AVMC de 0,8 (n=11) a los 6 meses. Además, la DCE media fue de 2.580 (más menos, 185) células/mm2 antes y de 1.310 (más menos, 740) células/mm2 a los 6 meses de la operación (n=13). Conclusiones: DMEK permite una rápida y casi completa rehabilitación visual. La DCE postoperatoria observada es comparable al obtenido con técnicas precedentes de queratoplastia endotelial(AU)

Purpose: To assess the clinical outcomes of DMEK in the first series of 120 eyes operated for the treatment of Fuchs endothelial dystrophy in terms of visual acuity and endothelial cell density. Methods: The first 120 consecutive eyes that underwent DMEK (i.e. transplantation of an isolated donor Descemet membrane with its endothelium) were evaluated. In all eyes, the best corrected visual acuity (BCVA) before and at 1, 3 and 6 months after surgery, as well as the endothelial cell density (ECD) before and at 6 months were measured. Results: In eyes with a functional DMEK graft and good visual potential (n=96), the BCVA was major or equal 20/40 (major or equal 0.5) in 77% after 1 month, 92% after 3 months, and 95% after six months; major or equal 20/25 (major or equal 0.8) in 50%, 63%, and 73% of the cases, and major or equal 20/20 (major or equal 1.0) in 23%, 34%, and 45% of the cases at 1, 3, and 6 months respectively. In this group, ECD averaged 2610 (more less 185) cells/mm2 before, and 1770 (more less 520) cells/mm2 at six months after surgery (n=96). In 15 eyes, a secondary Descemet stripping endothelial keratoplasty (DSEK) was performed. In this group, 91% of patients reached a BCVA of major or equal 20/40 (major or equal 0.5) and only one patient achieved a BCVA of 0.8 at 6 months after surgery (n=11). Furthermore, ECD averaged 2580 (more less 185) cells/mm2 before and 1310 (more less 740) cells/mm2 at six months (n=13). Conclusion: DMEK provides a fast and high visual rehabilitation. Endothelial cell density loss may be similar to earlier types of endothelial keratoplasty(AU)

Closed-chamber pulling-injection system for donor graft insertion in endothelial keratoplasty.

I describe the closed-chamber pulling-injection (CCPI) technique to improve surgical control and safety of graft insertion into the anterior chamber during Descemet-stripping automated endothelial keratoplasty (DSAEK). In CCPI, the graft is rolled up (endothelium facing inward) in a closed transparent insertion device, allowing it to be drawn into a well-formed anterior chamber and unfolded smoothly. The technique has been used successfully to treat corneal decompensation in 72 consecutive cases. The results indicate that using the CCPI technique, both average and complicated cases can benefit from the numerous advantages provided by endothelial keratoplasty.

Descemet's stripping endothelial keratoplasty under topical anesthesia.

We describe a technique for performing Descemet's stripping endothelial keratoplasty under topical anesthesia and report the results in 7 patients. No patient reported intraoperative discomfort, and no operative complications were noted. Using a topical anesthetic approach in appropriate patients eliminates the risks associated with retrobulbar and peribulbar blocks.

Long-term outcome of iron-endocytosing cultured corneal endothelial cell transplantation with magnetic attraction.

The long-term efficacy and safety of transplanting iron-endocytosing cultured corneal endothelial cells (CECs) with magnetic attraction were evaluated. Rabbit corneas were subjected to cryo-injury to detach CECs. Cultured rabbit CECs (RCEC) were exposed to spherical iron powder and then injected into the anterior chamber, after which a neogium magnet was fixed on the eyelid for 24 hr to attract the cells to Descemet's membrane (RCEC-iron group, n=4). An RCEC group (cryo-injury and injection of normal cultured RCEC, n=4) and a Cryo group (cryo-injury without injection of RCEC, n=4) served as controls. Intraocular pressure was measured for 12 months after surgery. Corneal findings on slit lamp biomicroscopy, RCEC density, the electro-retinogram (ERG), and residual iron in the ocular tissues were evaluated at final assessment. Intraocular pressure did not increase in any group throughout 12 months of observation. At the final assessment, the average corneal edema score of the RCEC-iron group was significantly lower than that of the RCEC or Cryo groups (p=0.021). The average CEC density of the RCEC-iron group was 2581+/-230 cells mm(-2) (mean+/-SD), whereas no CECs were observed on the inner surface of the central cornea in the RCEC and Cryo groups. No significant differences of the ERG (a- and b-wave amplitudes, and b-wave/a-wave ratio) were detected among the groups. Iron powder was not detected by Berlin blue staining in the ocular tissues of the RCEC-iron group. Apoptotic cells were not observed in the endothelium by terminal transferase-mediated nick-end labeling. Transplanted iron-endocytosing RCEC remained viable for 12 months after surgery. There were no detectable ocular complications after the transplantation of iron-endocytosing cultured RCEC. Magnetic attachment of iron-endocytosing CECs can be an effective and safe method for corneal endothelial repair.

Anomalia de Peters: tratamento clinico-cirúrgico e estimulação visual / Peter's Anomaly: clinical and surgical treatment and visual stimulation

Objetivo: Relatar o caso de uma paciente portadora de Anomalia de Peters submetida a tratamento clínico e cirúrgico e posterior estimulação visual precoce, freqüentemente esquecida e importante para integrá-la na sociedade não privando seu desenvolvimento neuropsicomotor. Local: Fundação Altino Ventura, Recife - Pernambuco. Método: Relato do caso. Resultado: A paciente, portadora de Anomalia de Peters, foi submetida a tratamento cirúrgico (trabeculotomia) em ambos os olhos, não sendo eficaz no olho direito que necessitou de nova intervenção cirúrgica (trabeculectomia com mitomicina). Posteriormente, com auxílio de medicação, a pressão intra-ocular foi controlada sendo, então, realizada estimulação visual precoce. Conclusão: Após estabilização da pressão intra-ocular com os procedimentos cirúrgicos e clínicos a paciente apresentou boa evolução na acuidade visual com a estimulação, enquanto aguarda o transplante de córnea (necessário pela opacificação), não a privando de desenvolver sua visão e tampouco de integrá-la na sociedade.

The corneal stroma: an inhomogeneous structure.

PURPOSE: This study was conducted to determine the elemental composition of the human cornea. Special attention was paid to corneal stroma inhomogeneity. METHODS: Seventy human corneas were examined by means of energy-dispersive X-ray analysis. Epithelium, subepithelium, middle stroma, sub-Descemet layer, Descemet's membrane and endothelium were subjected to repeated measurements. RESULTS: In the cellular layers the phosphorus concentrations were high [0.35 mol/kg dry weight (dw) in the epithelium and 0.403 mol/kg dw in the endothelium]. Similar concentrations were found for sulphur (0.38 mol/kg dw in the epithelium). Stromal layers showed high contents of sulphur: 0.26 mol/kg dw. The phosphorus concentration was found to be higher in the subepithelium than in the middle stroma. Sulphur concentrations were highest in Descemet's membrane, followed by the subepithelium and the middle stroma. DISCUSSION: Nucleic acids and energy-containing phosphates explain the high levels of phosphorus in the cellular layers. The high sulphur concentrations may be related to the phosphoadenosinphosphosulfate and protein turnover in the epithelium. We interpret the inhomogeneous distribution of phosphorus in the stroma as a function of the density of keratocytes. An evaluation of all known sulphur-containing biochemical components of the stroma (0.217 mol sulphur/kg dw) corresponds to our measurements. In contrast to former results we find the corneal stroma to be an inhomogeneous structure.

[Experimental alpha-chymotrypsin model of glaucoma in the rabbit: histopathological studies (author's transl)]. / Le modèle de glaucome expérimental à l'alpha-chymotrypsine chez le lapin: étude histologique.

The injection of alpha-chymotrypsin into the posterior chamber of the eye is known to produce an experimental ocular hypertension of long duration in animals. The present study reports the pathological changes which occur in the eye during the first nine months after the ocular injection of alpha-chymotrypsin in rabbits. Six weeks after treatment most of the eyes showed a buphthalmia and an intraocular pressure elevation which varied greatly from animal to animal. The anterior chamber angle of the treated eyes showed a progressive enlargement. Several days after the enzyme injection a transient increase in thickness of the cornea and Descemet membrane was noted. Cupping of the optic disc, characterized by a total disappearance of the optic nerve head fibers and an excavation beginning at margins of the retina appeared after four months and in most cases were present seven months after the treatment. More or less prominent retinal degeneration was also evidenced three months after enzyme injection. The results indicate alpha-chymotrypsin-induced occular hypertension in the rabbit leads after several months to pathological change in the eye analogous to that observed in human glaucoma.

Hyperbaric oxygen and corneal incision healing.

Corneal incision healing in the presence of daily or twice daily exposures to hyperbaric oxygen was compared in dogs to the natural course of such healing. Exposures lasted for 90 min and consisted of 60% oxygen administered at 60 fsw, an oxygen exposure of 2 ATA. Twenty corneas received such exposure, and 20 corneas were allowed to heal under natural conditions. Eyes were enucleated between 5 and 56 days after incision. The corneas were studied by gross observation and light microscopy. Uncomplicated and essentially comparable healing of the incisions occurred. There was a suggestion that superficial central clearing of the incision opacity occurred more quickly in the hyperbaric oxygen series.

Experimental alphachymotrypsin glaucoma.

Experimental glaucoma was produced in 50% of rabbit eyes by injecting 75 units of alphachymotrypsin into the posterior chamber. The elevation of intraocular pressure was stable, rarely exceeded 50 mm Hg, and lasted one year or longer. Progressive buphthalmos first appeared 2 to 3 weeks following injection of the enzyme. Ocular histologic changes included bullous keratopathy, iris and ciliary body atrophy, and cupping of the optic disc. The optic nerve became atrophic but no cavernous degeneration occurred. In the retina there was thinning of the nerve fiber layer and loss of ganglion cells with preservation of the other retinal elements. The mechanism leading to glaucoma following alphachymotrypsin injection is unclear. This study demonstrated formation of peripheral anterior synechiae and reduction of outflow facility within 2 weeks following injection and these factors may play a role.

Diagnosis and Treatment of Congenital Glaucoma

The term congenital glaucoma is used to indicate a state of raised introcular pressure due to an intrauterein disturbance and menifest at or shortly after birth. DIAGNOSIS: Dicision as to the presence or absence of primary congenital glaucoma (buphthalmos) in infants is not always easy. Correct diagnosis and further dicision as to the proper form of treatment necessitates considering all the factors. Early signs; 1. Epiphera, photophobia and blepharospasm. 2. Corneal edema. 3. Corneal enlargement. 4. Tears in Descemet's membrane. 5. Deep anterior chamber. 6. Cupping and atrophy of optic discs. Late signs; Late changes are the result of progression of earlier signs. Examination. Office examination. Examination under general anesthesia. 1. External examination. 2. Corneal diameter measurement. 3. Intraocular pressure and facility of outflow. 4. Ophthalmoscopy. 5. Gonioscopy. TREATMENT: Medical; Surgical; 1. Goniotomy. 2. Goniopuncture. 3. Fistulizing procedure. 4. Cyclodiathermy. 5. Cyclocryotherapy.